CNSC-14. GLIOBLASTOMA MULTIFORME TUMOR VOLUME AND PERSISTENCE OF CHIMERIC ANTIGEN RECEPTOR T CELLS FOLLOWING TREATMENT

Abstract Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR)-expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, and lymphoblastic leukemias suggesting benefits in GBM. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure. A radiology software known as the mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). Fluorescence-activated cell sorting (FACS) analysis takes a sample mixture of cells and sorts them into different populations based on specific biomarkers and characteristics. B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume (3.04% Subject 001 with 2438 mm² volume and 2.38% Subject 003 with 224 mm² tumor volume). However, the number of CAR-T cells per 1 mm² was significantly reduced in patients with a larger post-surgical tumor volume (0.0012 cells/mm² Subject 001 and 0.010 cells/mm² Subject 003). This study shows that although there is an overall increased CAR-T cell persistence for a larger tumor volume, the number of CAR-T cells per 1 mm² is significantly smaller for larger tumor volumes, while illustrating that a larger post-surgical tumor bulk volume is correlated with an increased CAR-T cell persistence within 1-week post-infusion. These findings provide novel information and complement other correlative studies as part of the Phase 1 interventional clinical trial for glioblastoma patients.