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Gene therapy is fighting to enter mainstream medicine. With sickle cell disease, the fight is heating up.

Roughly two years ago, the FDA made the historic decision to approve the first gene therapy in the US, finally realizing the therapeutic potential of hacking our biological base code after decades of cycles of hope and despair. Other approvals soon followed, including Luxturna to target inherited blindness and Zolgensma, a single injection that could save children with a degenerative disease from their muscles wasting away and dying before the age of two.

Yet despite their transformative potential, gene therapy has only targeted relatively rareand often fataldisorders. Thats about to change.

This year, a handful of companies deployed gene therapy against sickle-cell anemia, a condition that affects over 20 million people worldwide and 100,000 Americans. With over a dozen therapies in the run, sickle-cell disease could be the indication that allows gene therapy to enter the mainstream. Yet because of its unique nature, sickle-cell could also be the indication that shines an unflinching spotlight on challenges to the nascent breakthrough, both ethically and technologically.

You see, sickle-cell anemia, while being one of the worlds best-known genetic diseases, and one of the best understood, also predominantly affects third-world countries and marginalized people of color in the US. So far, gene therapy has come with a hefty bill exceeding millions; few people afflicted by the condition can carry that amount. The potential treatments are enormously complex, further upping costs to include lengthy hospital stays, and increasing potential side effects. To muddy the waters even more, the disorder, though causing tremendous pain and risk of stroke, already has approved pharmaceutical treatments and isnt necessarily considered life-threatening.

How we handle gene therapies for sickle-cell could inform many other similar therapies to come. With nearly 400 clinical trials in the making and two dozen nearing approval, theres no doubt that hacking our genes will become one of the most transformative medical wonders of the new decade. The question is: will it ever be available for everyone in need?

Even those uninterested in biology have likely heard of the disorder. Sickle-cell anemia holds the crown as the first genetic disorder to be traced to its molecular roots nearly a hundred years ago.

The root of the disorder is a single genetic mutation that drastically changes the structure of the oxygen-carrying protein, beta-globin, in red blood cells. The result is that the cells, rather than forming their usual slick disc-shape, turn into jagged, sickle-shaped daggers that damage blood vessels or block them altogether. The symptoms arent always uniform; rather, they come in crisis episodes during which the pain becomes nearly intolerable.

Kids with sickle-cell disorder usually die before the age of five; those who survive suffer a lifetime of debilitating pain and increased risk of stroke and infection. The symptoms can be managed to a degree with a cocktail of drugsantibiotics, painkillers, and a drug that reduces crisis episodes but ups infection risksand frequent blood transfusions or bone marrow transplants. More recently, the FDA approved a drug that helps prevent sickled-shaped cells from forming clumps in the vessels to further combat the disorder.

To Dr. David Williams at Boston Childrens Hospital in Massachusetts, the availability of these treatmentshowever inadequatesuggests that gene therapy remains too risky for sickle-cell disease. Its not an immediately lethal diseaseit wouldnt be ethical to treat those patients with a highly risky experimental approach, he said to Nature.

Others disagree. Freeing patients from a lifetime of risks and pain seems worthy, regardless of the price tag. Inspired by recent FDA approvals, companies have jumped onto three different treatments in a bitter fight to be the first to win approval.

The complexity of sickle-cell disease also opens the door to competing ideas about how to best treat it.

The most direct approach, backed by Bluebird Bio in Cambridge, Massachusetts, uses a virus to insert a functional copy of the broken beta-globin gene into blood cells. This approach seems to be on track for winning the first FDA approval for the disorder.

The second idea is to add a beneficial oxygen-carrying protein, rather than fixing the broken one. Here, viruses carry gamma-globin, which is a variant mostly present in fetal blood cells, but shuts off production soon after birth. Gamma-globin acts as a repellent that prevents clotting, a main trigger for strokes and other dangerous vascular diseases.

Yet another idea also focuses on gamma-globin, the good guy oxygen-carrier. Here, rather than inserting genes to produce the protein, the key is to remove the breaks that halt its production after birth. Both Bluebird Bio and Sangamo Therapeutics, based in Richmond, California, are pursing this approach. The rise of CRISPR-oriented companies is especially giving the idea new promise, in which CRISPR can theoretically shut off the break without too many side effects.

But there are complications. All three approaches also tap into cell therapy: blood-producing cells are removed from the body through chemotherapy, genetically edited, and re-infused into the bone marrow to reconstruct the entire blood system.

Its a risky, costly, and lengthy solution. Nevertheless, there have already been signs of success in the US. One person in a Bluebird Bio trial remained symptom-free for a year; another, using a CRISPR-based approach, hasnt experienced a crisis in four months since leaving the hospital. For about a year, Bluebird Bio has monitored a dozen treated patients. So far, according to the company, none has reported episodes of severe pain.

Despite these early successes, advocates worry about the actual impact of a genetic approach to sickle-cell disease.

Similar to other gene therapies, the treatment is considered a last-line, hail Mary solution for the most difficult cases of sickle cell disease because of its inherent risks and costly nature. Yet end-of-the-line patients often suffer from kidney, liver, and heart damages that make chemotherapy far too dangerous.

Then theres the problem of global access. Some developing countries, where sickle-cell disease is more prevalent, dont even have consistent access to safe blood transfusions, not to mention the laboratory equipment needed for altering blood-producing stem cells. Recent efforts in education, early screening, and prevention have also allowed people to live longer and reduce the stigma of the disorder.

Is a $1 million price tag ever attainable? To combat exhorbitant costs, Bluebird Bio is offering an installment payment plan for five years, which can be terminated anytime the treatment stops working. Yet for patients in South Africa, India, or Cambodia, the costs far exceed the $3 per month price tag for standard treatment. Even hydroxyurea, the newly-approved FDA drug to reduce crisis pain episodes, is just a fraction of the price tag that comes with gene therapy.

As gene therapy technologies are further refined and their base cost reduced, its possible that overall costs will drop. Yet whether these treatments will be affordable in the long run remains questionable. Even as scientists focus on efficacy rather than price tag, NIH director Dr. Francis Collins believes not thinking about global access is almost unethical. There are historical examples for optimism: vaccines, once rather fringe, now touch almost every corner of our world with the help of scientific knowledge, advocacy groups, andfundamentallyproven efficacy.

With the rise of gene therapy, were now in an age of personalized medicine beyond imagination. Its true that perhaps sickle-cell disease genetic therapies arent quite there yet in terms of safety and efficacy; but without tackling access issues, the therapy will be stymied in its impact for global good. As genetic editing tools become more powerful, gene therapy has the potential to save even more livesif its made accessible to those who need it most.

Image Credit: Image by Narupon Promvichai from Pixabay

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Gene Therapy for Sickle-Cell Anemia Looks Promisingbut It's Riddled with Controversy - Singularity Hub

The "Hematopoietic Stem Cell Transplantation (HSCT) Market" report contains data that has been carefully analyzed in the various models and factors that influence the industrial expansion of the Hematopoietic Stem Cell Transplantation (HSCT) market. An assessment of the impact of current market trends and conditions is also included to provide information on the future market expansion. The report contains comprehensive information on the global dynamics of Hematopoietic Stem Cell Transplantation (HSCT), which provides a better prediction of the progress of the market and its main competitors [Regen Biopharma Inc, China Cord Blood Corp, CBR Systems Inc, Escape Therapeutics Inc, Cryo-Save AG, Lonza Group Ltd, Pluristem Therapeutics Inc, ViaCord Inc]. The report provides detailed information on the future impact of the various schemes adopted by governments in different sectors of the world market.

The Hematopoietic Stem Cell Transplantation (HSCT) market report is crafted with figures, charts, tables, and facts to clarify, revealing the position of the specific sector at the regional and global level. The report also provides a brief summary of all major segments, such as [Autologous], with more detailed market share data in terms of supply, demand, and revenue from trading processes and after-sales.

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The Hematopoietic Stem Cell Transplantation (HSCT) report rates the market according to different segments, including geographic areas [Peripheral Blood Stem Cells Transplant (PBSCT), Bone Marrow Transplant (BMT), Cord Blood Transplant (CBT)] and current market trends. The market report contains information about different companies, manufacturers and traders.

The market report comprises an analysis of the latest developments in the field of innovative technologies, detailed profiles of the industry's top competitors, and an excellent business model. The report also contains information on market expectations for the coming years. The Hematopoietic Stem Cell Transplantation (HSCT) report also provides a detailed summary of the macro and microelement estimations that are important to market participants and newly developed companies.

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The different characteristics and performance of Hematopoietic Stem Cell Transplantation (HSCT) are analyzed based on subjective and quantitative techniques to give a clear picture of current and future evaluation.

Research Objective :

Our board of exchange givers additionally as exchange experts over the value chain have taken immense endeavors in doing this gathering activity and hard work add request to deliver the key players with helpful essential and optional information concerning the world Hematopoietic Stem Cell Transplantation (HSCT) advertise. moreover, the report furthermore contains contributions from our exchange experts that may encourage the key players in sparing their time from the inside examination half. firms WHO get and utilize this report will be totally benefitted with the derivations conveyed in it. but this, the report furthermore gives top to bottom investigation on Hematopoietic Stem Cell Transplantation (HSCT) deal in addition on the grounds that the elements that impact the customers additionally as undertakings towards this technique.

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Hematopoietic Stem Cell Transplantation (HSCT) Market Expected to Deliver Dynamic Progression until 2028| Regen Biopharma Inc - The World Industry...

Myelodysplastic syndrome (MDS) is a blood disorder caused due to the production of abnormal blood cells in bone marrow. Bone marrow failure leads to drop in the number of healthy blood cells in the body. In MDS, bone marrow does not produce healthy red blood cells, white blood cells, and/or platelets. Symptoms of MDS in the beginning are no specific than causes of pancytopenia i.e., deficiency of RBC, WBC and platelets. Therefore, the final diagnosis of MDS is done after examination of the cells of bone marrow.

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Bone marrow sample is taken from inside of a bone (usually the hip bone) and examined with a microscope using special stains to look for abnormal and immature cells. According to the American Cancer Society, over 13,000 new cases of MDS occur in the U.S. each year. According to the National Organization for Rare Disorders, 30% of patients with MDS can develop a form of blood cancer known as acute myeloid leukemia. Majority of patients diagnosed with MDS are aged between 65 and 70; however, MDS can affect people of any age and the risk of developing MDS increases with age.

The global myelodysplastic syndrome treatment market is driven by rise in the global geriatric population as MDS is most commonly found in this population and remains an incurable disease. Moreover, significant progress has been made in the diagnosis of MDS with the help of sequencing technologies. Chromosomal abnormalities can be identified in MDS patients with these technologies. These are useful for both diagnosis and prognosis in MDS patients. For instance, patients with chromosome 5q deletions are more likely to respond to lenalidomide. No new drugs have been approved for MDS by the U.S. Food and Drug Administration since 2006. Current available therapies can be efficacious, but are generally not curative. Some of the challenges in developing new treatments are the complexity and heterogeneity of MDS as a disease.

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The global myelodysplastic syndrome treatment market can be segmented based on type of treatment and region. In terms of type of treatment, the market can be classified into supportive therapy, growth factors, chemotherapy (including hypomethylating agents), and stem cell transplant. Cytarabine, azacitidine, decitabine, and lenalidomide are the major drugs used during chemotherapy.

Stem cell transplant is the only cure for MDS; however, majority of patients are not treated with stem cell transplant due to various factors such as high treatment cost, transplant-related deaths, and relapse rate at five years (as high as 40%). The chemotherapy segment is expected to hold major share of the global myelodysplastic syndrome treatment market due to larger application and less complications than other therapies such as stem cell transplant.

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Geographically, the global myelodysplastic syndrome treatment market can be segmented into North America, Europe, Asia Pacific, Latin America, Africa, and Middle East. North America is projected to dominate the global myelodysplastic syndrome market during the forecast period due to factors such as the rise in aging population and growing awareness about the disease among the population coupled with unmet medical needs in this region.

Key players operating in the global myelodysplastic syndrome treatment market are Celgene Corporation, Otsuka Holdings Co., Ltd., Sandoz, Inc., Dr. Reddys Laboratories, Inc., Accord Healthcare Ltd., Mylan N.V., and Pfizer, Inc.

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Myelodysplastic Syndrome Treatment Market Assessment Latest Insights on Trends and Challenges - Techi Labs

ESPCs derived from pig provide important implications for developmental biology, organ transplantation, regenerative medicine, disease modeling, and screening for drugs.

FREMONT, CA: Stem cell therapy, usually applied to humans, is now extended to animals too. It is a regenerative treatment applied to cats, dogs, pigs, and other animals. It includes removing cells from bone marrow, blood or fat, umbilical cords, and the cell can grow into any kind of cell and can repair damaged tissues. The regenerative therapy has been successful in animals. It can be used mainly for the treatment of spinal cord and bone injuries along with the problems with tendons, ligaments, and joints. One of the breakthroughs is the embryonic stem cell lines obtained from the pig.

Scientists have derived Expanded Potential Stem Cells (EPSCs) from pig embryos for the first time. They offer the groundbreaking potential to study embryonic development and produce translational research in genomics and regenerative medicine. Embryonic stem cells (ESC) are derived from the inner cells of early embryos called blastocysts. They are pluripotent cells as they can develop into various cell types of the body in the culture dish. The newly derived porcine EPSCs isolated from pig embryos are the first well-characterized cell lines worldwide. Their pluripotent ability provides important implications for developmental biology, organ transplantation, regenerative medicine, disease modeling, and screening for drugs.

The stem cells can renew themselves, showing that they can be kept in culture indefinitely while showing the typical morphology and gene expression patterns of embryonic stem cells. Because somatic cells have a limited lifespan, they cannot be used for such applications, and therefore the new stem cells are better suited for the lengthy selection process. These porcine stem cell lines can easily be edited with new genome editing techniques like CRISPR/Cas, and are currently the simplest, most versatile and precise method of genetic manipulation.

The EPSCs have a greater capacity to develop into numerous cell types of the organism as well as into extraembryonic tissue, the trophoblasts, rending them very unique and, thus, their name. This capacity is valuable for the future promising organoid technology where organ-like small cell aggregations are grown in 3D aggregates and used for research into early embryo development, various disease models, and testing of new drugs in Petri dishes. Also, they offer a unique possibility to investigate functions or diseases of the placenta in vitro.

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How Will Animals Get Benefitted by Stem Cell Therapy? - Medical Tech Outlook

VALLEY COTTAGE, N.Y. Stem cells are undifferentiated biological cells, and having remarkable potential to divide into any kind of other cells. When a stem cell divides, each new cell will be a new stem cell or it will be like another cell which is having specific function such as a muscle cell, a red blood cell, brain cell and some other cells.

There are two types of stem cells

Stem cells harvested from umbilical cord blood just after birth. And this cells can be stored in specific conditions. Stem cells also can be harvest from bone marrow, adipose tissue.

Embryonic cells can differentiate into ectoderm, endoderm and mesoderm in developing stage. Stem cells used in the therapies and surgeries for regeneration of organisms or cells, tissues.

Stem cells are used for the treatment of Gastro intestine diseases, Metabolic diseases, Immune system diseases, Central Nervous System diseases, Cardiovascular diseases, Wounds and injuries, Eye diseases, Musculoskeletal disorders.

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Harvesting of Adult cell is somewhat difficult compare to embryonic cells. Because Adult cells available in the own body and it is somewhat difficult to harvest.

Stem Cell TherapiesMarket: Drivers and Restraints

Technology advancements in healthcare now curing life threatening diseases and giving promising results. Stem Cell Therapies having so many advantages like regenerating the other cells and body organisms. This is the main driver for this market. These therapies are useful in many life threatening treatments. Increasing the prevalence rate of diseases are driven the Stem Cell Therapies market, it is also driven by increasing technology advancements in healthcare. Technological advancements in healthcare now saving the population from life threatening complications.

Increasing funding from government, private organizations and increasing the Companies focus onStem cell therapiesare also driven this market

However, Collecting the Embryonic Stem cells are easy but Collecting Adult Stem cell or Somatic Stem cells are difficult and also we have to take more precautions for storing the collected stem cells.

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Stem Cell TherapiesMarket: Segmentation

Stem Cell Therapies are segmented into following types

Based on treatment:

Based on application:

Based on End User:

Stem Cell TherapiesMarket: Overview

With rapid technological advantage in healthcare and its promising results, the use of Stem Cell Therapies will increase and the market is expected to have a double digit growth in the forecast period (2015-2025).

Stem Cell TherapiesMarket: Region- wise Outlook

Depending on geographic regions, the global Stem Cell Therapies market is segmented into seven key regions: North America, South America, Eastern Europe, Western Europe, Asia Pacific excluding Japan, Japan and Middle East & Africa.

The use of Stem Cell Therapies is high in North America because it is highly developed region, having good technological advancements in healthcare setup and people are having good awareness about health care. In Asia pacific region china and India also having rapid growth in health care set up. Europe also having good growth in this market.

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Stem Cell TherapiesMarket: Key Players

Some of the key players in this market are

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By Aprille HansonAssociate Editor

Aprille Hanson

Deacon Butch King and his wife Debbie (left) stand with their daughter Paula Draeger (center) in front of the Seed of Hope garden at UAMS Winthrop P. Rockefeller Cancer Institute in Little Rock Dec. 4. Last month, King was able to place a seed of hope token into the garden, signifying he is cancer-free, thanks to a stem cell donation from his daughter.

Aprille Hanson

Deacon Butch King and his wife Debbie (left) stand with their daughter Paula Draeger (center) in front of the Seed of Hope garden at UAMS Winthrop P. Rockefeller Cancer Institute in Little Rock Dec. 4. Last month, King was able to place a seed of hope token into the garden, signifying he is cancer-free, thanks to a stem cell donation from his daughter.

Deacon Butch King was given a gift in 2017. He was diagnosed with a rare disease MDS/MPN, myelodysplastic/myeloproliferative neoplasm-unclassifiable to be exact.

The hybrid disease results when bone marrow overproduces unhealthy blood cells, according to University of Arkansas for Medical Sciences in Little Rock.

The diagnosis sent the family on a harrowing journey for the next two and a half years: four changes of insurance coverage and medical facilities, 19 rounds of chemotherapy, 430 lab results, 14 bone marrow biopsies, 11.25 gallons of donated blood and the disease progressing to Acute Myeloid Leukemia.

Looking at a deadly disease as a gift takes a radical faith in God, one that King and his wife Debbie have carried with grace to his cancer-free diagnosis Nov. 4.

It was given to us as a gift. And how do we manage gifts? We care for them, we nurture them, we polish them, show them off with pride and we give thanks to God. Those are his words, our words together. We had a gift and we had to manage it, we didnt get a choice, his wife said.

King was ordained a deacon in 2012, serving at Immaculate Conception Church in North Little Rock. The couple has four children, 12 grandchildren and six great-grandchildren, with another on the way in March. After 23 years of serving in the U.S. Air Force working in secure communications, he spent 22 years with the U.S. Postal Service.

In October 2016, he had a metal stent placed in his heart and could not have any surgeries for the following six months. In November of that year, he twisted his knee at work. When he was finally ready to have knee surgery in May, his lab work was irregular. In June they learned he had developed a rare blood disorder, MDS, which later in the year progressed to MPN. It required a stem cell transplant, with only a 30 percent chance of surviving a transplant.

I was kind of stunned at first, King said. As a deacon, he had been used to visiting the sick in nursing homes and hospitals.

This is one of the stories you can say, I know how you feel because Ive been there or were praying for you and really mean it, he said.

With every roadblock of insurance not covering the procedure or a hospital turning the transplant down because he was high risk, faith prevailed.

In December 2017, their youngest daughter Paula Draeger, 38, was a perfect match for a stem cell transplant, an extremely rare result.

OK, we can do this; were going to heal him. Weve got the perfect match. If this doesnt work, nothing will. So that was just kind of the reaction, lets do it, the married mother of two said.

Debbie King said, Shes a Spina bifida baby. We were told that she would be a vegetable when she had her spinal surgery. So shes a miracle to be here; long before this ever came God had a plan.

Once Medicare kicked in, insurance would cover a transplant if a clinical trial was available. It led the family to 13 visits to University of Oklahoma Stephenson Cancer Center in Oklahoma City, though they refused the transplant.

Debbie King said they specifically chose Oklahoma City because the family had been, and still are, praying daily for Blessed Stanley Rothers intercession.

The martyr, who grew up on a farm in Okarche, Okla., was declared blessed on Sept. 23, 2017, in Oklahoma City. He was killed in 1981 while serving his people in Guatemala.

He needed a miracle. And we said God provides miracles, Debbie King said.

Before we started any treatment we would place the entire illness and what would be happening at Blessed Stanley Rothers gravesite in Oklahoma City, visiting 11 times, she said.

Whats the miracle? The miracle is the faith. And thats what Butch has said, she said.

On March 13, the Kings were told they wouldnt be continuing the trial in Oklahoma.

We were ready to just be on maintenance and enjoy the days we had, she said. On March 14, our 44th wedding anniversary we were celebrating what we thought could be our last one.

But Dr. Appalanaidu Sasapu, hematologist oncologist with the UAMS Stem Cell Transplantation and Cellular Therapy Program, never gave up on them. Because Kings disease had progressed to leukemia in April, the stem cell procedure could now be done at UAMS and covered by insurance.

Draeger said the stem cell donations, done over a weekend via a port, were simple, with no side effects aside from building her energy up in the following week.

For what youre able to give somebody, what you have to endure pales in comparison to what hes been through and what you can give him, she said.

King no longer has the blood disease and is cancer free, though he will continue at least a years worth of chemotherapy treatments.

Since his diagnosis, they attend the smaller St. Patrick Church in North Little Rock for Mass, but he cannot yet return to ministry.

We do our prayer time in the mornings and evenings, we count our blessings every night before we go to bed and we just know, what was our blessing today? Did we see somebody that we havent seen before that God put in our path? Is it a new doctor who is going to take this on? King said.

But through this whole process weve been truly blessed, had no regrets. If I had to do it over, if thats the path of my life that God wants me to take, then Ill do it.

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Deacon Butch King learns to accept the 'gift' of cancer - Arkansas Catholic

LentiGlobin, Bluebird Bios investigational gene therapy for sickle cell disease (SCD), continues to show promising results in SCD patients participating in the companys Phase 1/2 HGB-206 clinical trial, according to the latest study data.

The new findings which included data from additional patients treated in the trial, updated data from those previously reported, and exploratory analyses were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition, held Dec. 6-10 in Orlando, Fla.

LentiGlobinisa gene therapy that has been developed to increase the levels of hemoglobin the protein that transports oxygen in the blood in people with SCD.

The therapy works by delivering functional copies of a modified form of the beta-globin gene (A-T87Q-globin gene) into patients red blood cell precursors, known as hematopoietic stem cells, or HSCs. Once these precursors differentiate, their red blood cells start producing a modified version of hemoglobin, called HbAT87Q.

By boosting the production of this anti-sickling form of the protein, LentiGlobin reduces the proportion of defective hemoglobin in patients red blood cells. That, in turn, reduces the sickling and destruction of these red blood cells and other complications associated with SCD.

The safety and efficacy of LentiGlobin is currently being evaluated in three groups identified as A-C of SCD patients participating in Bluebirds ongoing open-label, Phase 1/2 HGB-206 trial (NCT02140554).

Those in group A were treated per the original trial protocol. Meanwhile, those in groups B and C received an enhanced treatment protocol, approved in 2016, that is designed to increase the therapys efficiency. In groups A and B, patients HSCs were extracted from the bone marrow, while in group C, they were extracted from the blood.

As of the data cutoff date of August 26, 2019, seven participants in group A, two in group B, and 17 in group C had been treated with LentiGlobin. According to new data presented at the meeting, only two patients from group A required regular blood transfusions after the treatment.

In addition, the updated findings revealed that the levels of anti-sickling HbAT87Q remained stable in all participants from groups A and B over a post-treatment follow-up period of three years. Similarly, levels of total hemoglobin also were found to have remained stable in both patient groups over a two-year follow-up.

At the trial participants last visit, the median levels of anti-sickling HbAT87Q were 0.9 g/dL among those from group A, and 3.6 g/dL and 7.1 g/dL in the two patients from group B. The median levels of total hemoglobin were 9.0 g/dL among patients from group A, and 11.3 g/dL and 13.0 g/dL among those from group B.

Normal levels of hemoglobin in the blood range from 12.5 to 17.5 g/dL.

Among 12 patients from group C who were followed for at least six months, the median levels of anti-sickling HbAT87Q made up at least 40% of their total hemoglobin. At their last visit, the levels of anti-sickling HbAT87Q ranged from 2.7 to 9.0 g/dL, and the levels of total hemoglobin from 9.3 to 15.2 g/dL.

In groups A and B, LentiGlobin reduced the frequency of painful vaso-occlusive crises (VOCs) and acute chest syndrome (ACS) in the two years following treatment.

Nine patients from group C who were followed for at least six months had experienced four or more VOCs or ACS episodes in the two years prior to receiving LentiGlobin. Treatment with the gene therapy led to a reduction of 99% in the frequency of annual VOCs and ACS. In this group, there were no reports of ACS or severe VOCs for up to 21 months following treatment.

Moreover, among those from group C, LentiGlobin reduced the levels of different markers of red blood cells destruction, including reticulocytes, lactate dehydrogenase (LDH), and bilirubin.

LentiGlobins safety profile was consistent with previous data. No serious adverse events related to treatment were reported during the study. Only one mild, non-serious event of hot flush was found to be related to LentiGlobin. That event was rapidly resolved and did not require treatment.

Exploratory analyses were performed in a sub-group of patients from all three groups. In 12 participants who had been followed for at least six months, more than 70% of the individuals red blood cells were found to contain the anti-sickling HbAT87Q at the last study visit, these analyses showed. Moreover, in four of these patients, nearly all their red blood cells (90%) were positive for HbAT87Q.

In addition, exploratory analyses revealed that participants red blood cells were less prone to sickling following treatment with LentiGlobin.

At ASH, the growing body of data from our clinical studies of LentiGlobin for SCD reflects results from 26 treated patients with up to four years of follow-up, David Davidson, MD, Bluebird Bios chief medical officer, said in a press release.

We continue to observe patients treated in Group C producing high levels of gene-therapy derived anti-sickling hemoglobin, HbAT87Q, accounting for at least 40% of total hemoglobin in those with six or more months of follow-up, and exploratory assays show that HbAT87Q is present in most red blood cells of treated patients, Davidson said.

The robust production of HbAT87Q was associated with substantial reductions of sickle hemoglobin, HbS, as well as improvement in key markers of hemolysis [red blood cells destruction]. Most importantly, patients in Group C have not experienced any episodes of acute chest syndrome or serious vaso-occlusive crises following LentiGlobin for SCD treatment, he added.

The company is recruiting participants with transfusion-dependent -thalassemia (TDT) for a Phase 3 trial (NCT03207009) testing LentiGlobin. Moreover, according to the companys pipeline, there is a Phase 2/3 trial planned in sickle cell disease for this gene therapy.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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LentiGlobin Gene Therapy Continues to Show Promising Results in SCD, Updated Trial Data Shows - Sickle Cell Anemia News

Led by researchers at Baylor College of Medicine, a study published in the journal Cell Stem Cell reveals a new mechanism that contributes to adult bone maintenance and repair and opens the possibility of developing therapeutic strategies for improving bone healing.

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized, said corresponding author Dr. Dongsu Park, assistant professor of molecular and human genetics and of pathology and immunology at Baylor. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum the outer layer of tissue that envelopes the bone. Previous studies have shown that these two populations of stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms.

Of the two, periosteum stem cells are the least understood. It is known that they comprise a heterogeneous population of cells that can contribute to bone thickness, shaping and fracture repair, but scientists had not been able to distinguish between different subtypes of bone stem cells to study how their different functions are regulated.

In the current study, Park and his colleagues developed a method to identify different subpopulations of periosteum stem cells, define their contribution to bone fracture repair in live mouse models and identify specific factors that regulate their migration and proliferation under physiological conditions.

Periosteal stem cells are major contributors to bone healing

The researchers discovered specific markers for periosteum stem cells in mouse models. The markers identified a distinct subset of stem cells that contributes to life-long adult bone regeneration.

We also found that periosteum stem cells respond to mechanical injury by engaging in bone healing, Park said. They are important for healing bone fractures in the adult mice and, interestingly, their contribution to bone regeneration is higher than that of bone marrow stem cells.

In addition, the researchers found that periosteal stem cells also respond to inflammatory molecules called chemokines, which are usually produced during bone injury. In particular, they responded to chemokine CCL5.

Periosteal stem cells have receptors molecules on their cell surface that bind to CCL5, which sends a signal to the cells to migrate toward the injured bone and repair it. Deleting the CCL5 gene in mouse models resulted in marked defects in bone repair or delayed healing. When the researchers supplied CCL5 to CCL5-deficient mice, bone healing was accelerated.

The findings suggested potential therapeutic applications. For instance, in individuals with diabetes or osteoporosis in which bone healing is slow and may lead to other complications resulting from limited mobility, accelerating bone healing may reduce hospital stay and improve prognosis.

Our findings contribute to a better understanding of how adult bones heal. We think this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties regulated by specific mechanisms, Park said. We have identified markers that enable us to tell bone stem cell subtypes apart and studied what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries.

Reference

Ortinau et al. (2019) Identification of Functionally Distinct Mx1+SMA+ Periosteal Skeletal Stem Cells. Cell Stem Cell. DOI: https://doi.org/10.1016/j.stem.2019.11.003

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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New Mechanism of Bone Maintenance and Repair Discovered - Technology Networks

DUBLIN--(BUSINESS WIRE)--The "Global Blood and Bone Marrow Cancer Treatment Market Size, Market Share, Application Analysis, Regional Outlook, Growth Trends, Key Players, Competitive Strategies and Forecasts, 2019 to 2027" report has been added to ResearchAndMarkets.com's offering.

The global blood and bone marrow cancer treatment market was valued at US$ 38.8 Bn in 2018 and is expected to reach US$ 74.9 Bn by 2027, expanding at a CAGR of 7.7% from 2019 to 2027.

Market Insights

Blood cancer begins in the bone marrow which is the integral source of stem cells which later are differentiated in different types of blood cells in the human body. Researchers at Bristol Myers Squibb Company have stated that approximately 1.85 million new cases of blood cancer will be diagnosed by 2040 throughout the globe.

Lymphoma is the largest indication segment for blood and bone marrow cancer treatment market. It is prevalent in 2 types Hodgkin lymphoma and Non-Hodgkin lymphoma throughout the globe. The chief variables responsible for its rising prevalence worldwide are increasing prescription of immunosuppressant drugs for treating chronic infections and genetic mutations. Leukemia occurs when the DNA of immature white blood cells gets damaged due to exposure to ionizing radiation, hazardous chemicals, smoking, etc. The prevalence rate of leukemia is highly variable across different ethnic groups with men to women ratio of 1.4.

Chemotherapy is reigning the therapy segment for blood and bone marrow cancer treatment market. The key parameter hold responsible for its increasing demand is the availability of its generic version at affordable cost, drastically reducing the healthcare burden on ailing patients. Oncologists prefer to use them in combination therapy either with radiotherapy or immunotherapy to treat patients showing resistance to first-line drug therapy. Immunotherapy will be the fastest-growing segment during the forecast period owing to its promising drug pipeline for the treatment of blood cancer.

North America representing a market share of 34.6% is dominating the regional segment for blood and bone marrow cancer treatment market. The chief contributing factor for its market supremacy is a growing incidence of blood cancer. As per the research citings of the Leukemia and Lymphoma Society (CDC) figures after every 3 minutes, 1 person in the U.S. is diagnosed with blood cancer. In 2019, approximately 176,200 people in the U.S. are diagnosed with blood cancer in the United States. Europe holds a market share of 30.8% owing to the supportive regulatory framework provided by the European Medical Agency for the development and sale of medication for the treatment of blood cancer. The Asia Pacific accounts for 18.4% market share on account of rising public health awareness related to blood cancer & its treatment and developing healthcare infrastructure.

Key Market Movements:

Key Topics Covered:

Chapter 1. Preface

1.1. Report Scope and Description

1.1.1. Purpose of the Report

1.1.2. Target Audience

1.1.3. USP and Key Offerings

1.2. Research Scope

1.3. Research Methodology

1.3.1. Phase I-Secondary Research

1.3.2. Phase II-Primary Research

1.3.3. Approach Adopted

1.3.4. Top-down Approach

1.3.5. Bottom-up Approach

1.3.6. Phase III-Expert Panel Review

1.3.7. Assumptions

1.4. Market Segmentation

Chapter 2. Executive Summary

2.1. Global Blood and Bone Marrow Cancer Treatment Market Portraiture

2.2. Global Blood and Bone Marrow Cancer Treatment Market, by Indication, 2018 (US$ Bn)

2.3. Global Blood and Bone Marrow Cancer Treatment Market, by Therapy, 2018 (US$ Bn)

2.4. Global Blood and Bone Marrow Cancer Treatment Market, by Geography, 2018 (US$ Bn)

Chapter 3. Blood and Bone Marrow Cancer Treatment Market: Dynamics and Future Outlook

3.1. Market Overview

3.2. Drivers

3.3. Challenges

3.4. Opportunities

3.5. Attractive Investment Proposition, by Geography, 2018

3.6. Competitive Analysis: Global Blood and Bone Marrow Cancer Treatment Market, by Key Players, 2018

Chapter 4. Global Blood and Bone Marrow Cancer Treatment Market, by Indication

4.1. Overview

4.2. Multiple Myeloma

4.3. Leukemia

4.4. Lymphoma

4.5. Others

Chapter 5. Global Blood and Bone Marrow Cancer Treatment Market, by Therapy

5.1. Chemotherapy

5.2. Immunotherapy

5.3. Stem Cell Transplant

5.4. Radiotherapy

5.5. Pipeline Analysis

5.5.1. Phase III Drug

5.5.1.1. Eltrombopag

5.5.1.2. Avatrombopag

5.5.1.3. Hetrombopag

5.5.1.4. Omidubicel

5.5.1.5. Fedratinib

5.5.1.6. ATIR101

5.5.1.7. Pegylated Proline Interferon Alpha-2b

5.5.2. Tabular Representation of Phase II and I Pipeline Drugs

Chapter 6. Global Blood and Bone Marrow Cancer Treatment Market, by Geography

6.1. Overview

6.2. North America Blood and Bone Marrow Cancer Treatment Market Analysis, 2017- 2027

6.3. Europe Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

6.4. Asia Pacific Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

6.5. Latin America Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

6.6. Middle East and Africa Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

Chapter 7. Company Profiles

7.1. AstraZeneca, Plc.

7.1.1. Business Description

7.1.2. Financial Information (Subject to data availability)

7.1.3. Product Portfolio

7.1.4. News Coverage

7.2. Celgene, Inc.

7.3. Bristol Myers Squibb & Company

7.4. Eli Lilly & Company

7.5. Johnson & Johnson Company

7.6. F.Hoffman La-Roche Ltd.

7.7. Merck & Co., Inc.

7.8. Novartis AG

7.9. Pfizer, Inc.

7.10. Varian Medical Systems, Inc.

For more information about this report visit https://www.researchandmarkets.com/r/pi0qoz

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Global Blood and Bone Marrow Cancer Treatment Market Trends & Analysis During the Forecast Period, 2019-2027 - ResearchAndMarkets.com - Business...

JSP191, a humanized antibody targeting CD117, is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplantation. The Phase 1 clinical trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that had poor outcomes.

Life-threatening disorders such as SCID, and other conditions including autoimmune diseases and hematologic cancers, can be cured by hematopoietic cell transplantation, and those with certain genetic diseases can be cured with stem cell-directed gene therapies. However, the number of patients who can benefit from these approaches is limited because of the severe toxicity of the chemotherapy used for pre-transplant conditioning that is needed to allow room in the bone marrow for the stem cells to engraft, said Judith Shizuru, M.D., Ph.D., co-founder and member of the Board of Directors of Jasper Therapeutics. We are encouraged by the initial Phase 1 study results of JSP191 in these fragile patients with SCID and plan to expand clinical development of this antibody beyond patients with SCID. We expect to initiate clinical trials of JSP191 in 2020 to evaluate it as a conditioning agent in patients undergoing hematopoietic cell therapy for acute myeloid leukemia, myelodysplastic syndrome and Fanconi anemia, and IND-enabling studies for sickle cell disease and autoimmune indications.

Details of the oral presentation follow:

Abstract Title: Non-Genotoxic Anti-CD117 Antibody Conditioning Results in Successful Hematopoietic Stem Cell Engraftment in Patients with Severe Combined Immunodeficiency (abstract #800) Session Name: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Innovative Approaches in Allogeneic Transplantation for Pediatric or Nonmalignant DisordersPresenter: Rajni Agarwal, M.D., Associate Professor of Pediatrics and Stem Cell Transplantation, the Stanford University School of MedicineTime: 3:00 p.m. ETLocation: W311EFGH, Level 3, Orange County Convention Center

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow is currently achieved by subjecting patients to toxic treatment with radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

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Jasper Therapeutics Announces Upcoming Data Presentation on Lead Program, JSP191, at 61st American Society of Hematology (ASH) Annual Meeting &...

DetailsCategory: DNA RNA and CellsPublished on Tuesday, 10 December 2019 10:25Hits: 254

GDA-201 demonstrated early evidence of clinical activity in patients with non-Hodgkin lymphoma, with multiple complete responses observed

Research on mechanism of action for the NAM technology platform provides further scientific rationale for stem cell engraftment and patient outcomes reported in previous Phase 1/2 clinical study of omidubicel

BOSTON, MA, USA I December 9, 2019 I Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to finding cures for blood cancers and serious blood diseases, today announced updated results from a Phase 1 clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), at the 61st Annual Meeting of the American Society of Hematology (ASH), which is being held December 710 in Orlando, FL. Data from 22 patients in the ongoing study showed GDA-201 in combination with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity in heavily pre-treated patients, including five complete responses observed among nine patients with NHL. Gamida Cell plans to initiate a Phase 1/2 multi-dose, multi-center study of GDA-201 in patients with NHL in 2020.

NK cells are increasingly recognized as a potential breakthrough approach in immunotherapy, and the data reported today provide early evidence that GDA-201 has the potential to be an important new treatment option, said Veronica Bachanova, M.D., Ph.D., Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota and principal investigator of the study through the Masonic Cancer Center. Given the population of heavily pre-treated patients with advanced disease, its particularly encouraging to witness multiple complete responses. I look forward to the continued development of this investigational therapy.

New research was also presented today on the mechanism of action of Gamida Cells NAM-based cell expansion platform, which is designed to enhance the number and functionality of allogeneic donor cells. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes observed in the Phase 1/2 clinical study of omidubicel, the companys advanced cell therapy currently in Phase 3 clinical development as a potential life-saving treatment option for patients in need of an allogeneic bone marrow transplant.

These mechanism of action data reinforce the transformative potential of our NAM therapeutic platform, which can be used to expand multiple cell types. Specifically for omidubicel, this research suggests that NAM modulates certain gene expression pathways that, collectively, mimic the hypoxic environment of the bone marrow to help preserve stem cell function and long-term engraftment ability, said Tracey Lodie, Ph.D., chief scientific officer of Gamida Cell. We expect to build on our findings by characterizing the metabolites produced when we expand stem cells to make omidubicel, and we are also beginning to conduct similar mechanism of action studies with GDA-201.

GDA-201 Phase 1 Clinical Data Presented at ASH

The oral presentation, Results of a Phase 1 Trial of GDA-201, Nicotinamide-Expanded Allogeneic Natural Killer Cells (NAM-NK) in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM) (Abstract #777), described data from the Phase 1 clinical study of GDA-201 in heavily pre-treated patients with advanced NHL and MM. Twenty-two patients were enrolled in the study, including nine patients with NHL and 13 patients with MM. Of these 22 patients, all were evaluable for safety and 21 were evaluable for response (NHL = 9; MM = 12).

In the study, cell therapy using GDA-201 with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity. Of the nine patients with NHL, five achieved a complete response and one achieved a partial response. Among the patients with MM, one patient achieved a complete response, and five patients achieved stable disease.

GDA-201 was generally well tolerated, with no graft vs. host disease (GvHD), no tumor lysis syndrome, no neurotoxicity and no marrow aplasia observed. No dose limiting toxicities were observed. Hypertension and hematologic events were the most common Grade 3/4 adverse events observed. Most non-hematologic toxicities were attributed to cyclophosphamide/fludarabine, which was used as a pre-conditioning treatment.

NAM Therapeutic Platform Mechanism of Action Data Presented at ASH

The poster presentation, Nicotinamide (NAM) Modulates Transcriptional Signature of Ex Vivo Cultured UCB CD34+ Cells (Omidubicel) and Preserves Their Stemness and Engraftment Potential (Abstract #3718), included transcriptome, transcription factor, and pathway analysis to elucidate the pathways leading to the preservation of engraftment after ex vivo expansion of CD34+ hematopoietic stem cells derived from umbilical cord blood (the starting point for omidubicel) compared to CD34+ cells grown in the absence of NAM.

Analyses showed that the presence of NAM reduced the expression of genes involved in the production of reactive oxygen and nitrogen species, suggesting that cell stress was minimized during expansion. In addition, NAM also decreased growth factor pathways responsible for activation and differentiation of hematopoietic stem cells, suggesting NAM expanded cells while keeping them in an undifferentiated state. The presence of NAM also led to a decrease in the expression of genes responsible for matrix-metallo proteinase secretion, simulating the microenvironment of the bone marrow. Additionally, NAM led to an increased expression of telomerase genes, which is believed to enable cells to remain in a more quiescent, stem-like state. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes that were observed in the Phase 1/2 clinical study of omidubicel.

About GDA-201 GDA-201 (formerly known as NAM-NK) is being developed as an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard-of-care antibody therapies. NK cells have the ability to kill tumor cells, representing a novel immunotherapeutic approach to cancer treatment. GDA-201 is designed to address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1 For more information on the clinical study of GDA-201, please visit http://www.clinicaltrials.gov.

About Omidubicel Omidubicel (formerly known as NiCord), the companys lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In a Phase 1/2 clinical study, omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated.2 A Phase 3 study evaluating omidubicel in patients with leukemia and lymphoma is ongoing in the U.S., Latin America, Europe and Asia.3 Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.4 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit http://www.clinicaltrials.gov.

GDA-201 and omidubicel are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

About the NAM Therapeutic Platform Gamida Cells proprietary NAM-based cell expansion platform is designed to enhance the number and functionality of donor cells in culture, enabling the creation of potentially transformative therapies that move beyond what is possible with existing approaches. The NAM therapeutic platform leverages the unique properties of nicotinamide to enable the expansion of multiple cell types including stem cells and natural killer (NK) cells with appropriate growth factors to maintain the cells original phenotype and potency. This can enable the administration of a therapeutic dose of cells with the potential to improve patient outcomes.

About Gamida Cell Gamida Cell is an advanced cell therapy company committed to finding cures for patients with blood cancers and serious blood diseases. We harness our cell expansion platform to create therapies with the potential to redefine standards of care in areas of serious medical need. For additional information, please visit http://www.gamida-cell.com.

1ClinicalTrials.gov identifier NCT03019666. 2 Horwitz M.E., Wease S., Blackwell B., Valcarcel D. et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Clin Oncol. 2019 Feb 10;37(5):367-374. 3 ClinicalTrials.gov identifier NCT02730299 4 ClinicalTrials.gov identifier NCT03173937

SOURCE: Gamida Cell

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Gamida Cell Announces Results from Phase 1 Study of GDA-201 and New Mechanism of Action Data at ASH 2019 Annual Meeting | DNA RNA and Cells | News...

PALO ALTO, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a new biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies, today announced the launch of the company with a $35 million total Series A financing. Abingworth LLP and Qiming Venture Partners USA served as lead investors, with further investment from Surveyor Capital (a Citadel company) and participation from Alexandria Venture Investments, LLC. The proceeds will be used to advance the clinical development of the companys lead product candidate, JSP191, which is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplant.

Jaspers development of JSP191 is also supported by a collaboration with the California Institute for Regenerative Medicine (CIRM), which has been funding the program and is committed to providing a total of $23 million in grant support. As part of the Series A financing, Amgen, which discovered JSP191 (formerly AMG191), has licensed worldwide rights to Jasper that also include translational science and materials from Stanford University.

Jasper was co-founded by Judith Shizuru, M.D., Ph.D., a hematopoietic stem cell transplant expert at Stanford University, and Susan Prohaska, Ph.D., a Stanford University-trained immunologist, stem cell biologist and early-stage drug development professional. Dr Shizurus CIRM-funded lab advanced the understanding of the ability of anti-CD117 to impact hematopoietic stem cells and, together with the Lucile Packard Childrens Hospital Stanford and University of California, San Francisco (UCSF) pediatric transplant teams, was the first to study an anti-CD117 antibody in the clinic as a conditioning agent. That humanized antibody, now called JSP191, was first studied for conditioning for transplant in immune-deficient patients in collaboration with Amgen, UCSF and CIRM.

Stem cell transplantation is a potential curative therapy for people with hematologic cancers, autoimmune diseases, and debilitating genetic diseases. However, the pre-transplant conditioning required to prepare patients for transplant involves highly toxic chemotherapy, which can be life-threatening and limits the number of people who are able to benefit, said Dr. Shizuru, co-founder and member of the Board of Directors of Jasper Therapeutics. JSP191 is the only anti-CD117 antibody to demonstrate safety and efficacy in severely ill patients receiving stem cell transplant in the clinic. We plan to expand clinical development to patients receiving transplants for acute myeloid leukemia/ myelodysplastic syndrome or autoimmune diseases and to patients receiving stem cell-directed gene therapies.

Dr. Shizuru added, With an experienced executive team of biotech veterans and a strong syndicate of healthcare-focused investors, Jasper Therapeutics is well positioned to achieve our vision of building a leading biotech company starting with JSP191 and expanding to other novel therapies for immune modulation, graft engineering and cell and gene therapies.

JSP191 is currently being evaluated in an ongoing Phase 1 clinical trial as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that failed. This severe genetic immune disorder leaves patients without a functioning immune system. Interim results of the study will be presented in an oral presentation (abstract #800) on Monday, December 9, at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Fla. Clinical studies to evaluate the safety and efficacy of JSP191 as a conditioning agent in patients undergoing hematopoietic cell therapy for hematologic cancers are planned for 2020.

Founding Management Team

Dr. Shizuru and Mr. Lis are joined on the Jasper Therapeutics Board of Directors by Kurt von Emster, Managing Partner of Abingworth LLP, and Anna French, Ph.D., Principal at Qiming Venture Partners USA. Dr. Prohaska is a Board observer.

With our investment in this program, were able to realize our mission of fast-tracking stem cell treatments by helping academic researchers rapidly advance the most promising discoveries in the lab into the clinics and to drug development with commercialization partners, said Maria T. Millan, M.D., President and CEO of CIRM. Jaspers two co-founders took a novel antibody with unique properties and moved it from the bench to the bedside relatively quickly, and were thrilled to partner with this talented team to potentially impact a broad group of people who could benefit from stem cell therapy.

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow is currently achieved by subjecting patients to toxic doses of radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

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Jasper Therapeutics Launches with $35 Million Series A Financing to Develop and Commercialize Innovative Conditioning Agents and Therapies to...

--(BUSINESS WIRE)--Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning agents and therapeutics to allow for expanded use of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

Company:

Jasper Therapeutics, Inc

Headquarters Address:

3000 Sand Hill Road B1-145

Menlo Park, CA

Main Telephone:

1-650-254-6687

Website:

https://jaspertherapeutics.com/

Type of Organization:

Private

Industry:

Biotechnology

Key Executives:

Executive Chairman and Interim Chief Executive Officer: William Lis

Chief Business Officer, Chief Financial Officer: Jeet Mahal

Company Contact

Contact:

Jeet Mahal

Phone:

1-650-254-6687

Email:

jmahal@jaspertherapeutics.com

Public Relations

Contact:

Julie Normart

Phone:

1-415-946-1087

Email:

jnormart@w2ogroup.com

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Company Profile for Jasper Therapeutics, Inc - Business Wire

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email. "Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville. "But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the U.S. and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris. "It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection. "You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers. They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the U.S.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

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2019: the year gene therapy came of age - Japan Today

DURHAM, N.C., Dec. 10, 2019 (GLOBE NEWSWIRE) -- Chimerix, Inc. (Nasdaq: CMRX), a biopharmaceutical company focused on accelerating the development of medicines to treat cancer and other serious diseases, today announced that data relating to its dociparstat sodium (DSTAT) program, formerly known as CX-01, were presented at the 61st American Society of Hematology Annual Meeting, in Orlando, FL.

The poster, titledUpdated Study Results for CX-01, an Inhibitor of CXCL12/CXCR4, With Azacitidine for the Treatment of Hypomethylating Agent Refractory AML and MDS, was presented byEric Huselton, M.D., Assistant Professor of Medicine at the University of Rochester on December 9, 2019.

As reported in the published study abstract, 20 patients with refractory myelodysplastic syndrome (MDS) (n = 9) or refractory acute myeloid leukemia (AML) (n = 11) were enrolled of which 15 were considered evaluable for response with a bone marrow biopsy after cycle 2. Patients received a 7-day continuous infusion of DSTAT (CX-01) at a dose of 0.25 mg/kg/hour, and azacitidine 75 mg/m2 daily days 1-7, in 28-day cycles. The primary objective of this trial was to assess the overall response rate. Half of the patients had high risk cytogenetic abnormalities and 3 had TP53 mutations. Patients had a median of 2 prior lines of therapy (range 1-3) with median of 6 prior cycles of hypomethylating agent (HMA) therapy (range 4-20). Only 4 patients had a confirmed response to prior HMA therapy.

The 15 evaluable patients received a median of 3 cycles of CX-01 and azacitidine (range 2-9). Of 15 evaluable patients, there was 1 CR (complete remission) and 3 bone marrow CRs (mCR, with incomplete peripheral blood count recovery), 9 stable disease, and 2 progressive disease for an overall response rate of 27%. Of the 3 patients with a mCR after cycle 2, two had hematologic improvement of their neutrophil and platelet counts, respectively, by the end of cycle 4. A patient with stable disease also had hematologic improvement in platelets.

The median overall survival of evaluable patients was 221 days. The median overall survival was not significantly different between AML patients at 221 days and MDS patients at 248 days.

Following a minimum of 4 cycles of prior HMA therapy, one would not expect to observe response to subsequent HMA therapy, said Dr. Huselton. These results demonstrate DSTATs potential to improve HMA therapy outcomes in terms of both response and overall survival.

"DSTATs mechanism of action is intended to enhance patient benefit when combined with an active agent, so to observe these results in HMA-refractory patients is promising. In addition to our planned Phase 3 pivotal trial in newly diagnosed AML, this study highlights the potential to develop DSTAT to enhance the benefit of multiple therapies such as azacitidine, in AML and MDS in both front-line and recurrent settings," said Mike Sherman, Chief Executive Officer of Chimerix.

AboutChimerix

Chimerixis a development-stage biopharmaceutical company dedicated to accelerating the advancement of innovative medicines that make a meaningful impact in the lives of patients living with cancer and other serious diseases. The two clinical-stage development programs are dociparstat sodium (DSTAT) and brincidofovir (BCV).

Dociparstat sodium is a potential first-in-class glycosaminoglycan biologic derived from porcine heparin that has low anticoagulant activity but retains the ability to inhibit activities of several key proteins implicated in the retention and viability of AML blasts and leukemic stem cells in the bone marrow during chemotherapy (e.g., CXCL12, selectins, HMGB1). Mobilization of AML blasts and leukemic stem cells from the bone marrow has been associated with enhanced chemosensitivity and may be a primary mechanism accounting for the observed increases in EFS and OS in Phase 2 with DSTAT versus placebo. Randomized Phase 2 data suggest that DSTAT may also accelerate platelet recovery post-chemotherapy via inhibition of platelet factor 4, a negative regulator of platelet production that impairs platelet recovery following chemotherapy. BCV is a lipid conjugate DNA polymerase inhibitor in development as a medical countermeasure for smallpox.For further information, please visit the Chimerix website,www.chimerix.com

CONTACT:

Investor Relations:Michelle LaSpaluto919-972-7115ir@chimerix.com

Will OConnorStern Investor Relations212-362-1200will@sternir.com

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Chimerix Presents Updated Results from Phase 2 Clinical Trial of DSTAT in Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia at American...

Using immunotherapy with genetically modified T cells that express chimeric antigen receptors or CARs designed to target tumor-associated molecules, have impressive efficacy in the treatment hematological malignancies.

A CAR is a synthetic construct that, when expressed in T cells, mimics T cell receptor activation and redirects specificity and effector function toward a specified antigen.[1]

In the treatment of cancer, this process is accomplished by linking an extracellular ligand-binding domain specific for a tumor cell surface antigen to an intracellular signaling module that activates T cells upon antigen binding.[1]

The presented studies include results from emerging second-generation cellular immunotherapy products that strive to overcome the limitations of existing products such as resistance and reduce toxicity and simplify treatment.

Cellular immunotherapy uses genetic engineering to enhance the ability of the immune system the bodys defense system against infection and disease to kill malignant cells in the blood, the bone marrow, and other sites, in order to keep cancer from coming back.

CAR T-cell TherapyChimeric antigen receptor T-cell therapies, better known as CAR T-cell therapies, are developed by harvesting a patients own T-cells, the immune systems primary cancer-killing cells, engineering them to target proteins specific to the surface of cancer cells, and reintroducing these modified T-cells back into the patients immune system to kill the cancer cells.

First generationFirst-generation CAR T-cell therapies primarily target CD-19, a protein found on the surface of most normal and malignant B cells in B cell cancers such as lymphoma. These therapies have been shown to produce long-term remissions in about one-third of patients with B-cell lymphomas that have not responded to prior therapies.

We are now seeing efforts to enhance the effectiveness of CAR T-cell therapy by designing products capable of attacking multiple targets, expand the availability of cellular immunotherapy to other blood cancers such as multiple myeloma and replace the complex manufacturing process required for CAR T-cell therapy with a uniform off-the-shelf product, noted Gary Schiller, MD, UCLA Health, an academic medical center which includes a number of hospitals and an extensive primary care network in the Los Angeles, California, region.

One of the phase I studies evaluates an off-the-shelf cellular immunotherapy product that targets two proteins found on the surface of lymphoma cells, including its potential to revive previously administered CAR T-cells that have stopped working.

Another study presents preclinical results for one of the first cellular immunotherapies to be based on off-the-shelf natural killer (NK) cells and the first, according to its manufacturer, to be genetically engineered to contain three active anti-tumor components.

The other two studies, also phase I studies, assess novel CAR T-cell therapies for multiple myeloma that test different dual-target strategies.

One investigational agent is genetically engineered to contain two proteins that attach to BCMA, a protein found almost exclusively on the surface of plasma cells, the immune-system cells that become cancerous in multiple myeloma.

The other is designed to target both BCMA and CD-38, another protein found on the surface of plasma cells. In both studies, many patients achieved minimal residual disease (MRD) negativity, which means that using highly sensitive testing fewer than one myeloma cell per 100,000 cells was identified in the bone marrow. Previous studies have shown that patients who achieve this milestone have a lower risk of relapse after more than three years of follow-up.

Dual-targeted CAR T-cell therapiesThe three phase I studies also hint at the possibility that dual-targeted CAR T-cell therapies might result in fewer patients experiencing moderate to severe cytokine release syndrome (CRS), a known adverse effect caused by an immune response in the body to the activated T cells that are attacking the cancer. CRS causes flu-like symptoms such as fever, body aches, and fatigue, and in severe cases can be life-threatening. Treatment with the drug tocilizumab can reduce CRS symptoms.

Dual-Targeted Antibody Elicits Durable ResponsesPatients with B-cell Non-Hodgkin Lymphoma (NHL) that had returned after or failed to respond to a median of three prior therapies showed complete responses (CR) and durable remissions after being treated with an investigational drug called mosunetuzumab (RG7828; Genentech/Roche). [2]

This investigational agent is a humanized, T-cell bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. The drug works by activating the patients own T-cells, stimulating them to attack and kill cancerous B cells to which they have been introduced by the novel antibody.

Mosunetuzumab simultaneously binds to CD3 epsilon (CD3), a component of the T-cell receptor (TCR) complex, and to CD20, a B-cell surface protein expressed in a majority of B-cell malignancies. This results in crosslinking of the TCR, inducing downstream signaling events that leads to B-cell killing.

Among patients whose lymphoma progressed after treatment with CAR T-cell therapy, 22% had complete remissions when treated with mosunetuzumab. This new drug targets two proteins, one on the surface of tumor cells and the other on the surface of the recipients Tcells.

Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T cells, noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T-cell therapy, he added.

The researchers observed many remissions continue after patients stop receiving the drug.

I have stopped therapy in some patients after six months and they have remained in remission. Some patients have remained in remission without additional therapy for more than a year, Schuster said.

New treatment options are needed not only for patients in whom CAR T-cell therapy has failed, but also for those patients whose lymphomas are getting worse so quickly that they cannot wait for CAR T-cell manufacturing, which takes several weeks, Schuster explained.

The data presented during the annual meeting of the American Society of Hematology included 270 patients (median age 62, 172 men) enrolled in the phase I trial in seven countries (the United States, Australia, Canada, Germany, South Korea, Spain, and the United Kingdom). All participating patients had B-cell lymphomas that had come back or not responded to a median of three prior therapies. Two-thirds of patients (67%) had fast-growing lymphomas; 85 (31%) patients had more slow-growing forms of the disease. In 30 patients (11%), the cancer was resistant to or returned after an initial response to CAR T-cell therapy; in 77 patients (29%), the disease had progressed after a stem cell transplant.

All patients were treated with mosunetuzumab by intravenous infusion. They had an imaging test at either six weeks or three months after starting therapy to assess the initial response to treatment, and responses continued to be followed every three months thereafter.

Forty-six of 124 patients with fast-growing lymphomas (37%) had measurable decreases in the extent of their cancer (objective response); 24 of 124 patients (19%) saw all detectable tumors disappear (complete response). A higher response rate was observed in patients with higher exposure to mosunetuzumab. Among patients with slow-growing lymphomas, 42 of 67 (63%) had objective responses and 29 of 67 (43%) had complete responses. Both objective response rate and complete response rate were maintained in subgroups of patients at high risk for relapse.

Complete remissions appear to be long lasting, Schuster said.

With a median follow-up of six months since first complete remission, 24 of 29 patients (83%) who achieved complete remissions of their slow-growing lymphomas and 17 of 24 patients (71%) who achieved complete remissions of their fast-growing lymphomas remain free of disease. In some patients whose cancers progressed after receiving CAR T-cell therapy, highly sensitive molecular testing showed that the previously administered CAR T cells increased in number.

This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR-T treatment, Schuster noted.

Cytokine-release syndromeIn this study, 29% of patients treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild.

Cytokine release syndrome or CRS is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. While most patients have a mild reaction, sometimes patients may have a severe, life threatening, reaction.

In 3% of patients, CRS was treated with tocilizumab (Actemra; Genentech/Roche). Four percent of patients experienced moderately severe neurologic side effects. Patients who received higher doses of mosunetuzumab were no more likely to have CRS or neurologic side effects than patients treated at lower doses.

A study of a higher dose of mosunetuzumab is now enrolling patients and long-term follow-up of these patients will ultimately help to better evaluate the durability of response data.

Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents, Schuster concluded.

Novel Off-the-Shelf CARPreclinical studies provide the first evidence that cellular immunotherapy for B cell cancers could ultimately become an off-the-shelf product, capable of being uniformly manufactured in large quantities as prescription drugs are.

We have taken the concept of traditional pharmaceutical drug development and applied it to cellular therapy, explained senior author Bob Valamehr, Ph.D, of Fate Therapeutics, a San Diego biopharmaceutical company.

The product called FT596, is among the first cellular immunotherapies to be based on off-the-shelf NK cells the first line of defense of the immune system and is the first cellular immunotherapy to be genetically engineered to contain three active anti-tumor components, Valamehr explained.

Comparable with standard CAR T-cell therapyFT596 demonstrated comparable ability to kill cancerous white blood cells as standard CAR T-cells and, when combined with the drug rituximab (Rituxan; Genentech/Roche), killed cancerous white blood cells that were no longer responding to standard CAR T-cell therapy due to loss of the CD19 antigen target.

The U.S. Food and Drug Administration (FDA) approved Fate Therapeutics Investigational New Drug Application for FT596 in September 2019 and the company hopes to begin a first-in-human phase I clinical trial for the treatment of B-cell lymphoma and chronic lymphocytic leukemia in the first quarter of 2020.

The primary purpose of this trial will be to assess the safety and activity of FT596 in patients.

ManufacturingThe development and manufacturing of FT596 begins with human induced pluripotent stem cells (iPSCs) that are uniquely capable of unlimited self-renewal and can differentiate into more than 200 types of human cells. These iPSCs are genetically engineered, after which a single genetically engineered cell or clone is selected and multiplied in the laboratory to create a master engineered cell line that can be repeatedly used to generate cancer-fighting immune-system cells such as NK and T cells.

Natural Kiler Cells or NK cells are a type of lymphocyte and a component of innate immune system, the bodys first line of defense against infection and disease. Unlike T-cells, which have to be trained to recognize their target and can kill only cells that display that target on their surface, NK cells do not need special preparation before going on the attack and can kill many different types of transformed or infected cells.

NK cells are multifaceted and can be viewed as a jack-of-all-trades when it comes to protecting the host, whereas T cells can act in only one way, Valamehr explained.

But NK cells are also different in other ways. They are inherently limited in their capacity to multiply and expand when infused into patients, and they have a shorter lifespan.

Valamehr and his colleagues used genetic engineering to address these shortcomings. In addition to engineering FT596 to carry a CAR targeting the CD19 protein, which is produced by nearly all B-cell lymphomas and leukemias, they inserted two other novel proteins: CD16, which boosts and broadens the NK cells ability to kill cancer cells, and IL15, which stimulates FT596 to proliferate and persist.

Valamehr explained that FT596 has been designed to address two more limitations of CAR T-cell therapy .

The investigational agent is an off-the-shelf product. As a result, it significantly improves the current patient-by-patient CAR T-cell treatment paradigm by eliminating the time-consuming and costly process that is currently required to treat a patient with CAR T-cells.

The addition of the CD16 protein gives FT596 broader therapeutic activity and versatility. In combination with rituximab, FT596 has the potential to lead to deeper and more durable responses and overcome resistance that hampers the long-term efficacy of CAR T-cell therapy.

Eliminating the high production cost, weeks of manufacturing time, and complex manufacturing process required for CAR T-cell therapy and replacing it with a mass-produced, off-the-shelf product, promises to expand access to effective cell-based cancer immunotherapy to many more patients who may benefit from it, Valamehr concluded.

Results from CARTITUDE-1 in R/R Multiple MyelomaPatients with multiple myeloma who had received a median of five prior therapies, and for whom standard-of-care treatments were no longer working, had a high response rate when treated with the investigational CAR T-cell therapy JNJ-68284528 (JNJ-4528), which targets BCMA, a protein commonly found on the surface of multiple myeloma cancer cells.

These patients participated in a clinical trials (NCT03548207), supported by Janssen Research & Development, designed to characterize safety of and establish the recommended Phase II dose (RP2D) (Phase Ib) and to evaluate the efficacy of JNJ-68284528 (Phase II).

We are seeing a high response rate, with most patients achieving MRD negativity, noted lead study author Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai in New York.

Considering these patients have all received multiple prior therapies, these results are extremely encouraging, Madduri added.

All evaluable patients receiving this CAR T-cell therapy have achieved MRD-negative disease state and 27 of 29 patients are progression free at a median follow-up of six months, Madduri said.

Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection. Typical signs and symptoms of multiple myeloma may be bone pain or fractures, high levels of calcium in the blood, kidney damage, and anemia. Multiple myeloma affects an estimated 160,000 people each year, occurs most often in people over 60. The disease is slightly more common in men than in women.

Although new therapies for multiple myeloma have recently become available that can extend patients life expectancy, a cure for the disease remains elusive.

We can get the disease into remission, but most patients unfortunately relapse, and outcomes are very poor for patients who have relapsed multiple times, she said.

Researchers explained that JNJ-4528 is a novel CAR T-cell therapy featuring two molecules that bind to BCMA, a protein found on the surface of multiple myeloma cells.

We are learning that every CAR T-cell therapy is different, Madduri said.

JNJ-4528 has a unique CAR T-cell composition in patients, preferentially enriched in CD8 T cells, which are believed to be one of the most important T cells in killing cancer cells, she noted.

This phase Ib/II trial is continuing to enroll patients.

During the 2019 annual meeting of the American Society of Hematology, Madduri reported results for the first 29 patients enrolled.

Patients T-cells were collected and sent to a laboratory where they were genetically engineered to express JNJ-4528. Prior to re-infusing these CAR T-cells, the patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells.

Following chemotherapy, each patient received a single infusion of the JNJ-4528 CAR T-cells.

After a minimum of 28 days, these patients had blood and bone marrow exams, which was followed by exams at six months, and one year after treatment to assess their response. The primary aims of the trial are to assess the therapys safety and to confirm the dose to be tested in a larger, phase II trial.

The median follow-up time in the current analysis is six months. Overall, 100% of patients had a clinical response to JNJ-4528. Moreover, 66% had a stringent complete response, meaning that sensitive laboratory and microscopic tests found no evidence for myeloma proteins or cells in blood, urine, or bone marrow.

Most patients (93%) experienced some form of CRS. One patient had severe (grade 3) CRS, and one patient died from its complications 99 days after the CAR T-cell infusion. In 76% of patients, CRS was treated with tocilizumab.

To see some patients in this heavily pretreated population surviving for a year or more with a one-time treatment and a manageable safety profile is remarkable, Madduri explained.

These patients feel that they have their quality of life back. They no longer have to come into the clinic for weekly treatments and some are well enough to travel, Madduri concluded.

The phase II portion of this study is ongoing to evaluate the overall response rate of patients treated with JNJ-68284528 (JNJ-4528). Additional clinical studies are evaluating the safety and efficacy of JNJ-4528 in different multiple myeloma treatment settings.

BreakthroughEarlier this week the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528).

The granting of Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528) is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech, noted Sen Zhuang, MD, Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development.

We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-68284528 (JNJ-4528) and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option, Zhuang concluded.

Encouraging Results for Dual-Targeted CAR T-Cell TherapyMore than three out of four patients with multiple myeloma that returned or did not respond to at least two therapies remained in remission seven months after treatment with a novel CAR T-cell therapy targeting two proteins that are frequently found on myeloma cells.

Nine patients experiencing sustained remissions in this study, which ws supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project fund of Hubei Province of China, and Cellyan Therapeutics, were diagnosed with a difficult-to-treat form of multiple myeloma in which the disease has spread beyond the bone marrow.

Roughly one in 10 patients with multiple myeloma develop tumors in the organs or soft tissues such as the blood vessels, muscles, and nerves. These so-called extramedullary tumors respond poorly to treatment, and patients who develop them have a poor outlook and poor health related quality of life (hrQoL)

Our results show that this CAR T-cell product can effectively achieve elimination of extramedullary tumors, said study author Yu Hu, MD, Ph.D, of Union Hospital, Huazhong University of Science and Technology in Wuhan, China.

Although these are preliminary data, they are encouraging for patients with multiple myeloma who have not responded to other therapies, Hu added.

Hu and his colleagues are developing the first CAR T-cell therapy to be genetically engineered to target BCMA and CD38, two proteins found on the surface of plasma cells. Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection and disease.

Our thinking was that targeting both of these proteins would improve treatment efficacy without increasing toxicity, and induce deeper, more durable remissions, Hu noted.

The first-in-humans phase I trial enrolled 22 patients whose average age was 59, of whom 11 were men. All had multiple myeloma that had returned or not responded to at least three therapies. Nine of the 22 patients had extramedullary tumors. The study aims were to determine the safest and most effective dose of the CAR T-cell therapy as well as to initially evaluate its effectiveness.

Just like in other trials with CAR T-cell therapies, the participating patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells. Then each patient was infused with the dual-targeted CAR T cells. Patients were divided into five groups, with each group receiving a higher dose than the previous one. Depending on the cell dose, patients received either one or two infusions.

At a median of 36 weeks of follow-up, 18 patients (90.9%) had MRD-negative disease. Twelve patients (54.5%) had a stringent complete response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a good or very good partial response, meaning that the level of M-protein (an abnormal protein produced by cancerous plasma cells) in the blood or urine was reduced but still detectable. In eight of the nine patients with extramedullary lesions, these tumors were undetectable on their computed tomography scans. For the 17 patients who remained in remission at seven months after treatment, the median duration of response was 28.8 weeks.

The adverse events observed included 20 patients who experienced CRS, of whom six needed treatment. No serious adverse neurologic effects such as seizures, movement impairment, difficulty speaking or understanding speech, or fatal swelling in the brain were reported.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu concluded.

The investigators continue to follow the patients for the next two years. They are also planning to conduct a phase II trial in both China and the United States to test the treatments effectiveness in a larger number of patients.

Clinical trialsA Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1) NCT03548207

References[1] Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol. 2018;200(2):459468. doi:10.4049/jimmunol.1701155 [Abstract][2] Schuster SJ, Bartlett NL, Assouline S, Yoon SS, Bosch F, Sehn LH, Cheah CY, Shadman M, et al. Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines. 61st annual meeting of the American Society of Hematology. Program: General Sessions. Session: Plenary Scientific Session. Hematology Disease Topics & Pathways: antibodies, Follicular Lymphoma, CRS, Diseases, Biological, Therapies, neurotoxicity, Adverse Events, CAR-Ts, Non-Hodgkin Lymphoma, DLBCL, immunotherapy, Lymphoid Malignancies. [Abstract][3] Goodridge JP, Mahmood S, Zhu H, Gaidarova S, Blum R, Bjordahl R, Cichocki F, et al. FT596: Translation of First-of-Kind Multi-Antigen Targeted Off-the-Shelf CAR-NK Cell with Engineered Persistence for the Treatment of B Cell Malignancies. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 625. Lymphoma: Pre-ClinicalChemotherapy and Biologic Agents: Targeting Apoptosis Pathways in Lymphoma.[Abstract][4] Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, Allred AJ, Banerjee A, et al. Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM). 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Novelty in CAR T in Relapsed/Refractory Multiple Myeloma. [Abstract][5] Li C, Mei H, Hu Y, Guo T, Liu L, Jiang H, Tang L, Wu Y, et al. A Bispecific CAR-T Cell Therapy Targeting Bcma and CD38 for Relapsed/Refractory Multiple Myeloma: Updated Results from a Phase 1 Dose-Climbing Trial61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Therapy for Relapsed Myeloma. Hematology Disease Topics & Pathways: Biological, Diseases, Adult, Therapies, Lymphoma (any), Adverse Events, CAR-Ts, Elderly, Biological Processes, Technology and Procedures, Cell Lineage, Study Population, Clinically relevant, Lymphoid Malignancies.

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ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment - OncoZine

Abstract

IFN- produced by T cells directly induces intestinal stem cell death upon inflammation-induced intestinal injury (see the related Research Article by Takashima et al.).

Intestinal regeneration upon tissue damage is fueled by intestinal stem cells (ISCs) residing in the crypt bottom of the epithelium and marked by the gene Lgr5 (1, 2). There is growing evidence that tissue repair is at least partially mediated by a regenerative inflammatory response (3, 4). How inflammation-induced intestinal injury influences ISCs and their microenvironment (stem cell niche) remains poorly understood. In this issue of Science Immunology, Takashima et al. (5) explore the changes in the ISC niche in vivo upon T cellmediated injury as a model of graft-versus-host disease (GVHD) and in vitro using organoid T cell cocultures. Although earlier studies already implicated interferon- (IFN-) as a negative regulator of intestinal epithelial homeostasis (68), Takashima et al. now demonstrate that IFN- directly acts on ISCs by triggering apoptosis.

In an allogeneic bone marrow transplant (BMT) model, Takashima and colleagues found that ISC numbers per intestinal crypt were markedly reduced in mice receiving bone marrow alone or bone marrow and T cells when compared with normal control mice. While the ISCs in the mice receiving only bone marrow recovered 7 days later, the ISC numbers remained reduced in those mice also transplanted with donor T cells. Of note, Paneth cell numbers were also reduced after ISC depletion. The numbers of organoids established from the intestines of mice 10 days after BMT recovered back to that of control mice, whereas the organoid forming capacity from crypts of mice after combined transplantation of bone marrow and T cells remained significantly lower. Similar in vivo and in vitro results were obtained when autoreactive T cells were transplanted, pointing to a common feature of T cellmediated intestinal injury.

As seen by three-dimensional confocal microscopy, intraepithelial T cells (CD3+ IELs) preferentially localized to the villus region, whereas lamina propriaassociated T cells (CD3+ LPLs) were equally distributed along the crypt-villus axis of control mice (Fig. 1A). Conversely, mice receiving bone marrow and allogeneic T cells showed a progressive increase in the density of both CD3+ LPLs and CD3+ IELs in the crypt region.

To identify signaling molecules that cause the loss of ISCs in this model, Takashima and colleagues performed several elegant murine and human epithelial organoid coculture experiments. Murine nave allogeneic T cells did not impair murine intestinal organoid numbers, whereas alloreactive T cells effectively reduced organoid numbers. Likewise, human allogeneic cytotoxic T cells robustly inhibited human intestinal organoid forming efficiency. Even bead-activated autologous T cells suppressed human intestinal organoid growth. The authors then proceeded to screen for potential pathways mediating cytotoxicity. Organoids cocultured with T cells in the presence of antiIFN- neutralizing antibodies showed normal growth. Although IFN- receptor (IFN-R)depleted T cells were still able to affect organoid viability, IFN-Rdepleted organoids were resistant to T cellmediated killing. Organoid toxicity by IFN- was also observed in the absence of T cells. Live imaging confirmed the progressive ISC depletion upon organoid exposure to IFN-. Treatment of organoids with the immunosuppressive JAK1/2 inhibitor ruxolitinib robustly preserved numbers of both organoids and ISCs in the presence of IFN-, irrespective of whether the organoids were cultured alone or together with T cells. The authors additionally demonstrated that JAK1-depleted organoids are resistant to IFN- treatment. Further downstream, ruxolitinib prevented STAT1 phosphorylation by IFN- in intestinal crypts, and, in line, STAT1-depleted organoids were resistant to growth suppression in response to IFN- treatment.

IFN-treated organoids showed reduced expression of ISC marker genes. ISCs underwent apoptosis in vitro in a direct response to IFN-. Next, the authors confirmed in vivo that ISC numbers did not change upon transplanting allogeneic bone marrow and T cells when treating mice with IFN- neutralizing antibodies. Likewise, ruxolitinib treatment protected ISCs from T cellmediated killing in vivo. Donor T cells, particularly T helper 1 cells, were activated and IFN-+. Transplanting IFN-depleted allogeneic T cells robustly reduced the ISC loss and allowed epithelial cell proliferation to increase.

Takashima and colleagues lastly investigated whether IFN- directly induces ISC apoptosis. Using tissue-specific depletion of IFN-R1, the authors found that epithelial loss of the receptor protects from the immune-mediated GVHD phenotype. IFN-R1 is expressed by both ISCs and Paneth cells, the epithelial component of the ISC niche (9). However, Paneth celldeficient organoids remained sensitive to both IFN- and allogeneic T cellmediated cytotoxicity. Likewise, T cells were able to reduce the number of organoids containing IFN-R1deficient Paneth cells, whereas organoids containing IFN-R1deficient ISC were protected from cytotoxicity. The authors demonstrated in further experiments that IFN- directly induces ISC apoptosis independent of Paneth cells (Fig. 1, B and C).

The study by Takashima et al. extends our knowledge on signaling between ISCs and immune cells, identifying ISCs as direct targets of IFN- secreted by T cells in immune-mediated intestinal damage (as caused by GVHD). In the 2015 study by Lindemans et al., this group already identified that interleukin-22 (IL-22) secreted by group 3 innate lymphoid cells (ILC3s) directly stimulates ISCs to proliferate and regenerate the intestinal epithelium upon inflammation-induced intestinal injury (4). Modulating the effects of T cellderived IFN- on ISC, for instance, by suppressing JAK/STAT signaling via ruxolitinib treatment, may provide a new therapeutic avenue to reducing GVHD-induced damage of the intestinal epithelium (10).

(A) ISCs maintain adult homeostasis of the intestinal epithelium. T lymphocytes patrol the intestine. (B) Takashima et al. show that in GVHD as modeled by BMT and aberrant activation of T lymphocytes, T cellderived IFN- directly acts on ISCs and induces apoptosis via JAK/STAT signaling. (C) Disease progression results in marked intestinal damage due to loss of ISCs and their niche.

Acknowledgments: Funding: K.K. is a long-term fellow of the Human Frontier Science Program Organization (LT771/2015). Competing interests: H.C. and K.K. are named inventors on patents or patents pending on Lgr5 stem cellbased organoid technology.

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IFN-: The T cell's license to kill stem cells in the inflamed intestine - Science

mohammad hassan 3 years and two months Image Credit:

Dubai: The father of a three-year-old boy in Dubai, whose only hope for survival is a bone marrow transplant, is desperately appealing for help.

Hafeez Khan, father of Mohammad Hassan, said the boy who is suffering from acute myeloid leukaemia (AML), needs Rs4.8 million (Pakistani) or Dh114,000 for his treatment, which includes one-two cycles of chemotherapy and a bone marrow transplant, in Pakistan.

Hassan, who has not been able to attend school as he has been in and out of hospitals in Dubai and Pakistan, was first diagnosed with AML when he was only a year and a half. He remained under treatment at a Dubai hospital for nearly a year until October 2018.

After a brief remission, he developed high fever and body pain on October 17 this year. When he did not respond to any regular medications, we took him to a Dubai hospital where his AML relapse was confirmed, said the father.

He said investigations revealed that Hassan had a soft tissue mass in his sinus which was diagnosed as a chloroma, a solid collection of leukemic cells occurring outside the bone marrow.

Khan, who works as a site engineer for a Dubai-based company, said, Hassan is my first born and I will do everything I can to save him. I appeal for any support that I can get towards this effort.

He said the child was earlier scheduled to have a bone marrow transplant in Turkey but due to the prohibitive costs, they were nowconsidering Pakistan. Still, the estimates we have been given are beyond our reach,Khan said, adding that he was praying for a miracle to save his son.

AML is one of the commonest types of leukaemia or blood cancer in children. In AML, the body makes many immature white blood cells. These cells, called myeloid blasts, cant mature into normal white blood cells. Although AML is a serious disease, it can be cured with high intensity chemotherapy and a bone marrow / stem cell transplant at an early stage.

mohammad hassan 3 years and two months Image Credit:

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3-year-old needs bone marrow transplant to survive, says UAE-based father - Gulf News

The first girl in the trial came in with chronic diarrhea and the immune system of an untreated HIV patient. Born with a rare genetic disease that impeded her ability to make B and T cells, she had once been given a stem cell transplant but it didnt take. Back in the hospital, she was injected with a new experimental antibody and then given a new stem cell transplant. Soon, she gained weight. The diarrhea stopped.

She has normal T cells now, Judith Shizuru, the Stanford scientist who pioneered the antibody, told Endpoints News. Shes in school.

Its the kind of medical story to launch a biotech around, and thats what Shizuruis doing. Today, her company Jasper Therapeutics is emerging out of stealth-mode with $35 million in Series A funding led by Abingworth and Qiming, a molecule from Amgen, and a Phase I trial set for its first readout on Monday at ASH.

Jasper is broadly aimed at making stem cell transplants safer, more accessible and more effective by using antibodies as conditioning agents. Theseagents clear out bone marrow to make room for the new stem cells to graft onto the body.

Their Phase I uses a naked antibody called JSP191 to help patients with severe combined autoimmune deficiency receive stem cell transplants the only possible cure for the life-threatening disease but such transplants are used in a wide variety of conditions and Jasper has broader aims. Those include other autoimmune diseases, acute myeloid leukemia and cell-directed gene therapy.

Theres a significant amount of progress being made in gene therapy, interim CEO William Lis told Endpoints, but no progress being made in a conditioning agent that will help graft gene therapy.

Shizuru path to the new antibody was long and fortuitous. In 1987, Arl Arzst, the legendary ad executive and president of Proctor and Gamble international flew in on a recruiting trip for Stanford business students. There he visited Shizuru, a young biologyPhD candidate, because he knew her roommate. Arzsts daughter had diabetes and as Shizuru explained the work she was doing on pancreatic islet cell transplants, he told her to come to Europe.

Shizuru had never been to Europe, but there Arszt introduced her to Ken Farber and the other founders of the Juvenile Diabetes Foundation (now the JDRF). The founders struck a years-long correspondence and encouraged Shizuru to go to medical school, where she decided that if scientists were ever going to develop transplants that didnt trigger an immune response, it would be through stem cell work. She continued her work at the Irv Weissman Stanford regenerative lab, where eventually a graduate student made a discovery that piqued her interest.

To put new stem cells in, you have to get the old stem cells out. Thats not always easy. The cells sit inthese pockets in the bone marrow, and theyre pretty comfortable there. Doctors have to force them out, often using chemotherapy or radiation, which damage DNA and cause severe side effects. The costs sometimes outweigh the benefits.

There are diseases were not treating because its too dangerous, Shizuru said. And the kids were treating, theyre so, so fragile.

The grad student had shown in mice that antibodies could be used to deplete the stem cells and potentially eliminate the need for chemotherapy or radiation. Shizuru and her team began looking to see if anyone had developed a human version of the antibody, CD117. It turned out Amgen had already developed a version of this antibody for a different use. It also turned out she had a former postdoc and a former advisor who worked there. They began a collaboration.

We set out to cross the valley of death, Shizuru said, using an industry slang term for the jump from animal models to human uses.

After making a variety of tweaks to the treatment, they published a paper inScience Translational Medicine in 2016showing the antibodies created a 10,000 fold reduction in the number of stem cells in mice.

The same year, they began a clinical trial on 90 SCID patients. These patients had received stem cell transplants when they were very young but hadnt been given chemo or radiation for fear the side effects would be too severe. The original transplants boosted their numberof immune cells, but without chemo or radiation, the stem cells dont graft into those pockets and the body wont continue producing T cells. Without those, they are extraordinarily prone to infection. Many pass away before age 2.

The hope is that the antibodies allowed the stem cells to graft, and the preliminary answer to that question will be out on Monday. For the first girl in the trial, life has improved but questions about how long her body will make immune cells remain. Still, for that girl and others, Shizuru is confident.

We see there is stem cell engraftment, Shurizi said. They are actually making new T cells.

Link:
Jasper Therapeutics launches out of Stanford with new approach to stem cell treatment - Endpoints News

Last week, a woman namedVictoria Gray became the first person in the U.S. to have her cells edited with CRISPR. The41-year-old patient was sufferingfromsickle cell anemia.

RELATED:FIRST HUMAN TRIAL USING CRISPR GENE-EDITING IN US BEGINS

The condition, caused by a genetic mutation that messes with the shape of red blood cells, causes havoc on patients, and to make things even worse, the options for treatment are very limited and ineffective. The only current treatment for sickle cell anemia patients is a donor transplant that works for just 10% of patients, but all that is about to change.

It was clear that analternative, much more effectivesolutionwas desperately needed. After much consideration, doctors believed that editing cells extracted from a patient's own bone marrow could restore effective red blood cell creation, and this is exactly the operation they attempted on Gray.

The doctors used CRISPR to tweak Gray's bone marrow DNA to turn on a specific protein that would allow proper red blood cell generation. The operation makes Gray the first person in the U.S. to undergo a CRISPR editing procedure and the second globally.

The treatment comes from observations made back in the 1940s.In 1941 a pediatrician named Jane Watson noticed that babies with sickle cell didnt have symptoms until 6 months to 1 year of age, Vivien Sheehan, a hematologist at Baylor University told Popular Science.

The pediatrician also discovered that these infants produced fetal hemoglobin for much longer periods than healthy babies.Following Watson's observations, the research since then has indicated that increasing fetal hemoglobin could provide an effective treatment for the disease.

Now, CRISPR may just make that treatment viable. But before we get too excited, it should be noted that the strategy comes with several risks.

In order for the edited cells to be inserted back into the patients bone marrow, other stem cells need to be deactivated. Otherwise, there is the chance the unedited stem cells may continue to produce sickled red blood cells very fast, outpacing the edited cells' production of healthy cells.

Now researchers say they need to follow Gray's progress for at least 15 years to rule out any other potential dangers of the procedure. Still, for those 90% suffering with sickle cell anemia that don't respond well to current treatment, the procedure, if successful, would offer the much-needed lifeline they've been hoping for.

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Sickle Cell Anemia Patient Becomes First Person in the US to Have Her Genes Edited With CRISPR - Interesting Engineering

This fall, 21-year-old Jurnee Farrell, a Howard University senior and a member of the universitys volleyball team donated stem cells to a complete stranger.

This fall, 21-year-old Jurnee Farrell, a Howard University senior and a member of the universitys volleyball team, was set to play in the Mid-Eastern Athletic Conference Tournament.

But instead, she was sidelined by a decision she made herself.

Two years ago, she signed up with Be the Match, a nonprofit that registers potential bone marrow and stem cell donors. When she got the call that she was a match for a 57-year-old woman with a form of leukemia, she was surprised.

At first I was like, This isnt real, Farrell recalled, but then said her decision was clear. She would follow through on the commitment she made two years ago when she signed up.

That meant undergoing a series of shots five days before the outpatient procedure, and then undergoing apheresis, a process in which the donor has blood removed through a needle in one arm, blood-forming cells are collected, and then the blood is returned through a needle in the other arm. The session can take up to eight hours.

Farrell said that the actual donation wasnt bad, but that the shots given in a series five days prior proved a little uncomfortable.

Nevertheless, she urges potential donors to sign up.

Its really not that bad, and the person whose life youre saving is probably going through so much more than you are, she said.

And while Farrell missed the tournament last month, shes back on the court already. We are going to the NCAA tournament this weekend, actually, and we play Pitt on Friday, she said. I just started practicing last week!

Farrells decision to register as a donor is one for which the staff at Be the Match is especially grateful.

Lauren Mueller, a public relations specialist with Be the Match, explained that for Caucasian patients waiting for a bone marrow or stem cell donation, the odds of finding a match are roughly 70%. For African-American patients, the odds are much lower, at 23%.

As a result, we are always looking to increase our diversity on the registry, said Mueller, who encourages people to consider registering.

It starts with a cheek swab, and Mueller said its not uncommon for years to go by before a potential donor hears that they might be a match, just as it was in Farrells case.

Your selfless action can help save a life, Mueller said.

Farrell said that shes hopeful her donation will prove successful, and that she would love to meet the recipient one day.

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Howard University athlete makes the call to donate stem cells - WTOP

WASHINGTON WhenHoward University student athlete Jurnee Farrellsigned up for the Be The Match registry during a Get In The Game campus drive, she didnt know if she would ever be called upon. However, when her phone rang two years later and she discovered she was a match for a 57-year-old woman suffering from acute lymphoblastic leukemia, she did not hesitate to participate.

The football team was hosting a Be The Match booth after Coach London had donated bone marrow to his daughter, recalls Farrell. I filled out a little form and turned it in. When I got the call a few months ago, they asked if I was still interested in donating. I didnt hesitate to say yes because this is somebodys life and there was no way I could say no to that.

Farrell is a senior criminology major from Denver, Colorado, and a member of the Howard University MEAC Championship Volleyball team. Wearing jersey No. 5 as a defensive specialist, Farrell is known for her bubbly personality off the court and her intensity on the court. At senior night, the day before her donation, the entire team rallied behind her in support of her decision. Unfortunately, the timing of the donation process meant that Farrell was not able to participate in this years MEAC playoffs with her teammates, who brought home their fifth MEAC championship on Nov. 24.

Of course, we were sad to miss out on having Jurnee play in the playoffs, but this is such a worthy cause and we were happy to support her all the way, saysHead Volleyball Coach Shaun Kupferberg.What she is doing speaks directly to Howard Universitys mission of truth and service, that each student comes here not only to learn, but to make a difference in the global community. Im extremely proud of her decision.

Thanks to several medical advances, the process to donate stem cells has drastically changed over the years. In addition to bone marrow donations, doctors can also use a stem cell procedure called Peripheral Blood Stem Cell (PBSC) donation through a short 4-hour out-patient procedure where blood is circulated from one arm, into a machine and then back into the donor.

Beth Carrion, account manager for Registry Growth and Development, says individuals like Farrell help to demystify the giving process and raise awareness of the need for a more diverse donor registry. The chances of finding a match for a stem cell transplant is dependent on a persons genetic markers. Outside of a family member, finding a donor within in ones ethnicity is the next viable option. According to Be The Match, each year approximately 14,000 patients are waiting for a transplant from someone outside of their family. The current odds to match a patient with a donor in one out of 430.

Be the Match is truly thankful for our partnership with Howard University because it plays a vital role in helping the African American community have a higher rate of finding a match, says Carrion. A white person in the registry has a 78 percent chance of finding a match. For Hispanics, its 46 percent, but for African Americans, its only a 23 percent chance. We look forward to hosting more events with Howard this spring.

One week after her procedure, Farrell is back at volleyball practice with her fellow teammates, preparing for the Tournament. As she looks to finish out her senior year, she says shes also hopeful that shell get to meet the woman she helped one day.

After the donation, I can have anonymous communication, but I cannot tell my identity. After a year, they will deem the transplant successful and then we can communicate, says Farrell. I for sure want to meet her.

To join the Howard University registry, text Howard to 61474, follow the prompts and a kit will be mailed to you. You may also register online atjoin.bethematch.org/howard.

# # #

Media Contact: Alonda Thomas,Alonda.Thomas@Howard.edu

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Howard University Student Gives a Stranger the Greatest Gift for the Holidays: Life - Howard Newsroom

AUTO1 shows 87% MRD negative complete response in adult patients with r/r ALL, with no severe cytokine release syndrome

Data presented at 61st American Society of Hematology Annual Meeting form basis for advancement of AUTO1 into pivotal clinical trial in adult ALL

Investor call to be held December 9 at 8:30 am ET / 1:30 pm GMT to review data

LONDON, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc(Nasdaq: AUTL) announced today new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia (ALL) and adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data were presented in oral presentations at the 61stAmerican Society of Hematology(ASH) Annual Meeting and Exposition inOrlando, FL. Additional data on pediatric patients with ALL will be presented on December 8.

The data on AUTO1 presented at this years ASH meeting demonstrate the favorable safety profile and high level of clinical activity of AUTO1 in both adults and pediatric patients with ALL, and we look forward to initiation of the pivotal program in adult ALL in the first half of 2020, said Dr. Christian Itin, chairman and chief executive officer of Autolus.

Acute Lymphoblastic Leukemia Data Presented

Title: AUTO1 A novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL (Abstract # 226)

Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie MB, PhD, FRCPath, honorary senior lecturer,Cancer Institute, University College London (UCL), in an oral presentation. The trial is designed to assess the primary endpoints of safety ( Grade 3 toxicity) and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden (44% had 50% BM blasts), who were considered high-risk for experiencing cytokine release syndrome (CRS). Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply.

As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 CRS, and 3 of 16 patients (19%), who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids.

Of 15 patients evaluable for efficacy, 13 (87%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% (2 of 15) patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 (100%) achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Adult ALL patients, who face a median survival of less than one year after their ALL recurs or relapses, have a significant need for a CAR T cell therapy that is highly active, safe and is a standalone therapy not requiring a stem cell transplant, said Dr. Hagop M. Kantarjian, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

The novel CD 19 CAR-T therapy, AUTO1, is potentially transformative as a standalone curative option for patients with r/r ALL, especially in adults, given its favorable safety profile, said Dr. Max Topp associate professor of Internal Medicine, Hematology and Oncology at the University of Wuerzburg.

Title: Therapy of pediatric B-ALL with a lower affinity CD19 CAR leads to enhanced expansion and prolonged CAR T cell persistence in patients with low bone marrow tumor burden, and is associated with a favorable toxicity profile (Abstract # 225)

Dr. Sara Ghorashian, honorary senior lecturer, Great Ormond Street Institute of Child Health, University College London, presented updated data from the phase 1 CARPALL study of AUTO1 in pediatric ALL patients with low bone marrow tumor burden. The trial is intended to assess the primary endpoints of safety and proportion of patients in molecular complete remission at 1 month. The study recruited a total of 25 patients and stratified them into 2 cohorts. Fourteen patients were treated in cohort 1, which utilized a manual manufacturing process; product was unable to be generated in 3 patients. Median follow-up was 27 months in cohort 1. Seven patients were treated in cohort 2, which utilized the semi-automated closed manufacturing process, which will be used for commercial supply. The aim of cohort 2 was to demonstrate feasibility of manufacture at scale. Product was generated for 100% of patients. Median follow-up was 7 months in cohort 2.

AUTO1 was well-tolerated overall, with no patients experiencing Grade 3 CRS and 1 of 21 (5%) experiencing Grade 4 neurotoxicity, which was considered unrelated to CAR T therapy.

Nineteen of 21 treated patients (90%) achieved molecular complete remission at 1 month post infusion. Consistent with pre-clinical data, CAR T cell expansion was excellent and detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at 1 month post infusion.

In the 14 patients in cohort 1, the overall survival at 6 months was 86% and at 12 months was 71%; event free survival (EFS) at 6 months was 71% and at 12 months was 54%. The patients in cohort 2 are not yet evaluable for these parameters. Overall, nine patients relapsed; 5 of 8 evaluable relapses were due to loss of CD19 antigen on the tumor cells.

Title: Clonal dynamics of early responder and long-term surviving CAR-T cells in humans (Abstract # 52)

Dr. Luca Biasco, senior research associate at University College London, presented a detailed analysis of CAR T products, and insertion site analysis from the CARPALL phase 1 patients. This analysis revealed highly polyclonal engraftment, even at very late time-points. Dr. Biasco hypothesized that the propensity for high level polyclonal long-term engraftment was due to favorable phenotype of the CAR T product and the binding kinetic of the receptor.

Diffuse Large B-cell Lymphoma Data Presented

Title: Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of cohort 1 and 2 of the ALEXANDER study (Abstract # 246)

Dr. Kirit Ardeshna, consultant hematologist, Department of Hematology, University College London Hospital NHS Foundation Trust, presented updated data from the ALEXANDER Phase 1/2 study of AUTO3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, in diffuse large B cell lymphoma (DLBCL). 16 patients were treated, and fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing Grade 3 CRS with primary treatment, and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Five of 14 had a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months.

DLBCL is an aggressive and rapidly progressing cancer, and early response is critical to ensuring positive outcomes for these patients. These early data show the promise of AUTO3 in DLBCL, and we expect to advance AUTO3 to a decision point in relapsed/refractory DLBCL by the middle of next year, said Dr. Christian Itin, chairman and chief executive officer of Autolus. In addition, we look forward to presenting the data from the AMELIA trial of AUTO3 in pediatric ALL during poster sessions on Sunday, December 8, 6:00 8:00 PM ET.

Investor call to review data on Monday, December 9

Autolus management will host an investor conference call on Monday, December 9, at 8:30 a.m. EDT/ 1:30pm GMT, to review the data presented at ASH.

To listen to the webcast and view the accompanying slide presentation, please go to:https://www.autolus.com/investor-relations/news-and-events/events.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9796038. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9796038.

About AUTO1

AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety - while maintaining similar levels of efficacy - compared to current CD19 CAR T cell therapies.Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells' abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights fromUCL Business plc(UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in pediatric ALL in the AMELIA clinical trial and in diffuse large B cell lymphoma in the ALEXANDER clinical trial.

AboutAutolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit http://www.autolus.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus financial condition and results of operations, as well as statements regarding the anticipated development of Autolus product candidates, including its intentions regarding the timing for providing further updates on the development of its product candidates, and the sufficiency of its cash resources. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed on November 23, 2018 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' future filings with the Securities and Exchange Commission from time to time. All information in this press release is as of the date of the release, and the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Investor and media contact: Silvia TaylorVice President, Corporate Affairs and Communications Autolus+1-240-801-3850s.taylor@autolus.com

UK:Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

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Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - GlobeNewswire

Cancer | One of the most common disease in the world

In what may prove as a breakthrough in the treatment of leukaemia and other blood diseases, scientists at UCLA have discovered a protein produced by a gene known as MLLT3 and its connection to the multiplication of human blood stem cells.

The discovery which was published in a study is very much significant as cancers such as leukaemia can be effectively treated using blood stem cells, also known as Hematopoietic stem cells (HSCs), produced outside the human body and could serve as an alternative to existing treatment options such as bone marrow transplants.

Self-renewal is the process by which stem cells divide to create more cells. The study focused on a specific type of the kind: Hematopoietic stem cells (HSCs) which are present within the bone marrow where along with self-renewal, they also produce different types of blood cells such as red and white by transforming into them.

Placing HSCs in laboratory dishes after their removal from the bone marrow causes then to lose their ability to self-renew, and they either transform into other blood types or perish. It is this process that the scientists studied. Through a series of steps, the researchers studied the genes that shutdown as the cells lost their capacity to self-renew.

They discovered that the HSCs' ability to self-renew corresponded with the expression of a gene called MLLT3. They also found that MLLT3 generated a protein that instructed HSCs to retain their capacity to self-renew. As the cells divide, the protein works along with other regulatory proteins to keep vital components of the HSCs' functioning.

Employing a viral vector the researchers tried to ascertain if maintaining the MLLT3 protein levels in lab dishes would help improve the self-renewing abilities of HSCs. A viral vector is a specially designed virus that transfers genetic information to the nucleus of a cell without giving rise to a disease. Using the vector, the scientists introduced an active MLLT3 gene into HSCs. They found that there was nearly a twelvefold multiplication of working HSCs in lab dishes.

"If we think about the amount of blood stem cells needed to treat a patient, that's a significant number," said Dr. Hanna Mikkola, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and senior author of the study, to the UCLA Newsroom.

The UCLA scientists observed that the use of 'small molecules' organic compounds that help in the multiplication of human HSCs, improved self-renewal in general. However, the cells were unable to maintain stable MLLT3 levels and did not perform well when implanted into mice.

"Our method, which exposes blood stem cells to the small molecules and also inserts an active MLLT3 gene, created blood stem cells that integrated well into mouse bone marrow, efficiently produced all blood cell types and maintained their self-renewing ability," said Vincenzo Calvanese, a UCLA project scientist and the study's co-corresponding author, to the UCLA Newsroom.

The team noted that the self-renewal of HSCs caused by MLLT3 was at a safe rate. This means that they did not acquire potent characteristics such as mutation or excessive multiplication, or the production aberrant cells that can cause leukaemia.

Determining which proteins and constituents within the DNA of the HSCs affect the activation and deactivation of MLLT3 is the next step for the team. Also, understanding the regulation of the process using components in the lab dishes is another step. The information gathered may help find ways in which MLLT3 could be switched on and off without employing a viral vector.

Read more:
Protein that can help treatment of leukemia identified, UCLA scientists upbeat - International Business Times, Singapore Edition

Hes done it - Stephen Armstrong has scooped a prestigious award for his huge fund raising efforts as his son fought a rare blood disorder.

The doting dad took home the award for Individual Fundraiser of the Year at the Anthony Nolan Supporter Awards 2019 ceremony held at the Tower of London.

The top awards were back for their seventh year to recognise the outstanding achievements of the volunteers, fundraisers and campaigners who help the pioneering blood cancer charity save lives.

And the award is in recognition of Stephens incredible fundraising efforts - leading a group of 19 friends and family in a series of physical challenges, all while his son Jacob was undergoing treatment.

When Jacob was diagnosed in 2017 at two-years-old, Stephen set out to find a matching stem cell donor, as well as raise awareness of the need for more people on the register.

From here Jacobs Journey was born, and through a series of challenges including the Great North Run, the Great North Bike Ride and climbing Ben Nevis, Stephen has helped raise over 20,000 for the charity.

Jacob is now four-years-old and his family have been told he does not need a transplant, but Stephen and his family want to continue raising awareness for others who arent so lucky.

When Jacob was diagnosed, we were stunned by how few people were on the stem cell donor register. I couldnt believe how a stranger in the street could potentially save our little boys life, said Stephen, 33, of Wallsend,North Tyneside.

On winning the award, Stephen said: I feel very proud- I really didnt expect it. You dont do it for recognition, but to get more people to join the register.

Stephen and mum Kirsty, 28, received the news in December 2017 that Jacob was suffering from bone marrow failure, which affects between 30 and 40 children each year.

They first became concerned about his health when they went abroad to get married and noticed he was getting bruised easily. The marks would take weeks to disappear, so when the couple returned to the UK they decided to take Jacob to the doctor for a check up.

After tests he was then diagnosed and was treated at the Great North Childrens Hospital in Newcastle, where he received two blood transfusions.

Stephen, who has raised a further 8,000 for other smaller charities, added: When we were told Jacob did not need the transplant it was the best news in the world, a total relief. He still needs check ups every three months and his consultants is keeping an eye on him. There are so few people on the stem cell donor register so I just wanted to create a ripple effect with awareness and get more people on it.

Henny Braund, Chief Executive at Anthony Nolan, said: Stephen is a hugely deserving winner of this award; his incredible support and passion for our work is a fantastic example of our charity, which is built on making lifesaving connections. It was lovely to meet Stephen and I continue to find myself inspired and humbled by the dedication and strength of supporters like him.

By raising vital funds and much needed awareness, we are curing blood cancer together. We can give families hope, and give more people a future. But without supporters like Stephen, lives cant be saved. Without him, there is no cure.

Anthony Nolan is the charity that finds matching stem cell donors for people with blood cancer and blood disorders and gives them a second chance at life. It also carries out ground-breaking research to save more lives and provide information and support to patients after a stem cell transplant, through its clinical nurse specialists and psychologists, who help guide patients through their recovery.

To see the full shortlist, and find out more about the charity visit the website here.

See more here:
Wallsend dad who called on the public for stem cells for his son scoops top Anthony Nolan Award - Chronicle Live