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Reworking Negative Receptor Signals for Improved Anti-Glioma T-cell Therapy

Meenakshi G. Hegde, MD

Dr. Hegde is an assistant professor in the Department of Pediatrics at the Baylor College of Medicine in Houston. Her SU2C Innovative Research Grant project, awarded in 2017, is titled “Reworking Negative Receptor Signals for Improved Anti-Glioma T-cell Therapy.”

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. Currently, the outlook for patients with GBM is poor: the five-year survival rate is less than 5 percent. Effective new therapies are urgently needed. Dr. Hegde and her team have utilized recent advances in cancer immunotherapy to generate chimeric antigen receptor (CAR) T cells that specifically recognize the human epidermal growth factor receptor 2 (HER2), a protein that is specifically associated with GBM. A phase I trial conducted by Dr. Hegde showed that HER2-CAR T cells presented no treatment-related toxicities, and offered clinical benefit to 50 percent of the patients treated. Thus, while HER2-CAR T cells have high therapeutic potential, there is a clear need to improve their anti-GBM activity. In this project, a sophisticated methodology developed by Dr. Hegde and her lab will enable the development of T cells able to kill GBM cells expressing HER2, and overcome/reverse the immune-inhibition of the tumor, with minimal toxicity. This study bears the potential to dramatically improve outcomes for GBM patients, and advance information leading to future standards in brain tumor immunotherapy.