Funded in partnership with the Cancer Research Institute through the V Foundation’s Virginia Vine event and Wine Celebration Fund-A-Need
Glioblastoma (GBM), the most common malignant brain tumor, is one of the most aggressive forms of cancer with limited therapeutic options and a dismal prognosis. The median survival of patients is 14.6 months. A significant barrier to treatment is the immunosuppressive tumor microenvironment (TME). A cancer vaccine is a form of immunotherapy that boosts the body’s defenses to fight cancer. We have developed personalized cancer vaccines based upon patient-specific neoantigens unique to a patient’s tumor to prime and boost immunity with the long-term goal to delay or prevent a recurrence. Twelve patients have been vaccinated with a peptide-based vaccine that incorporates up to ten personalized epitopes. Our preliminary results show induction of systemic immunity and an estimated favorable 6-month progression-free survival of 90.9% and 12-month survival from surgery date of 87.5%. We detected circulating antigen-specific cells in the blood that were apparent in ex vivo assays, suggesting priming of high-level responses. We now intend to apply new technologies (spatial sequencing, mass cytometry (CyTOF), imaging mass cytometry and O-link proteomics) to analyze the TME in GBM in depth, determine cross-talk of the tumor cells with the immune cells and other brain cells hijacked by the tumor to grow, and screen for circulating immune factors and their co-stimulatory and inhibitory molecules. The cellular and molecular profile and distribution of cells in the TME and the in-depth analysis of blood cells and soluble protein biomarkers will help predict response or resistance and identify new immunotherapy targets.
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