Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM (INTERCEPT)

Malignant primary brain tumors account for more human deaths than melanoma or cancer of the bladder or kidney. The non-specific nature of conventional therapy for brain tumors often results in incapacitating damage to surrounding normal brain and systemic tissue. Thus, in order to reduce off-site effects and be more effective, therapeutic strategies will have to target tumor cells precisely while minimizing collateral damage to the neighboring cerebral cortex. The goal of this protocol is to transfer autologous peripheral blood mononuclear cells (PBMCs) transduced with genes encoding a chimeric antigen receptor (CAR) that recognizes epidermal growth factor receptor variant III (EGFRvIII) tumor-specific antigen into patients with recurrent glioblastoma (GBM) following stereotactic radiosurgery (SRS). The CAR used will be targeted to a tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, which is expressed on a subset of patients. Normal PBMCs derived from patients with GBM will be genetically engineered with a viral vector encoding the CAR and infused directly into the patient’s tumor with the aim of mediating regression of their tumors. Despite our CAR being targeted to a tumor specific antigen, given the prior toxicity using CARs that were not targeted to tumor-specific antigens, the investigators have elected to begin with very low doses of cells.