Bench-to-bedside

Armed with this knowledge, further experiments showed that giving G-CSF, which is already used clinically as an immune system booster in cancer patients to mice with non-mutant IDH1 also increased their survival. And giving it in combination with the immune-stimulating gene therapy had an even bigger impact.

The team also confirmed that patients who have gliomas with mutated IDH1 also have higher levels of G-CSF circulating in their blood a clue that the findings will be applicable beyond the mouse models.

The next step, says Lowenstein, will be to work on moving these findings into a clinical trial, building on the current, ongoing trial using the immunotherapy/gene therapy combination.

Our study shows two main things: Patients with the IDH1 mutation may benefit from immunotherapy due to the G-CSF their tumors are producing, he said. And patients without the mutation may benefit from combining treatment with G-CSF and immunotherapy.

Additional authors include Brandon L. McClellan, Ruthvik P. Avvari, Rohit Thalla, Stephen Carney, Margaret S. Hartlage, Santiago Haase, Maria Ventosa, Ayman Taher, Neha Kamran, Li Zhang, Syed Mohammed Faisal, Felipe J. Nez, Mara Beln Garcia-Fabiani, Wajd N. Al-Holou, Daniel Orringer, Jason Heth, Parag G. Patil, Karen Eddy, Sofia D. Merajver, Peter J. Ulintz, Joshua Welch, Chao Gao, Jialin Liu and Gabriel Nez all of U-M; Shawn Hervey-Jumper of University of California, San Francisco; and Dolores Hambardzumyan of the Tisch Cancer Institute, Mount Sinai School of Medicine, New York.

Funding for the work was provided by National Institutes of Health and National Institute of Neurological Disorders & Stroke (R37-NS094804, R01-NS105556, R21- NS107894, R01- NS076991, R01-NS082311, R01-NS096756; the U-M Department of Neurosurgery; the Pediatric Brain Tumor Foundation, Leahs Happy Hearts Foundation, Ians Friends Foundation, Chad Tough Foundation, Pediatric Brain Tumor Foundation, and Smiles for Sophie Forever Foundation, National Cancer Institute (T32-CA009676), American Brain Tumor Association Basic Research Fellowship and a Rogel Cancer Center Scholar Award.

Paper cited: G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cells immunosuppression and enhances the efficacy of immunotherapy, Science Advances. DOI: 10.1126/sciadv.abh3243

Originally posted here:
Glioma subtype may hold the secret to the success of immunotherapies - Michigan Medicine

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