IMMU-07. CHECKPOINT MOLECULE B7-H3 IS HIGHLY EXPRESSED ON MEDULLOBLASTOMA AND PROVES TO BE A PROMISING CANDIDATE FOR CAR T CELL IMMUNOTHERAPY

Abstract BACKGROUND: B7-H3 (CD276) is a member of the B7 family of molecules involved in immune regulation and is over-expressed on a wide variety of solid tumor types. For this study we used a second-generation chimeric antigen receptor (CAR) T-cell targeting B7-H3 with the 41BB using a binder based on antibody MGA271. This CAR was previously created by the Mackall group and showed strong efficacy against an osteosarcoma model. The goal of this study was to test the anti-tumor function of the B7-H3 CAR in a myc-amplified highly aggressive medulloblastoma xenograft model. METHODS: We screened several medulloblastoma cell lines for B7-H3 expression and tested cytokine release (IL-2, TNF-α, INF-g) in vitro. Immunodeficient mouse xenograft models of a human Group 3, myc-amplified medulloblastoma cancer cell-line (D425) was used for in vivo efficacy studies. RESULTS: High expression of B7-H3 antigen was observed on various medulloblastoma cell lines (D425, MED8A, SU_MB002, D283, D341) and a freshly resected primary tumor sample classified as group 2 SHH subgroup. 24hr co-incubation of B7-H3 CAR T-cells and tumor cells resulted in a high cytokine release of IL-2, TNF-α, INF-g. Administration of a single intratumoral infusion of 1 x 106 B7-H3 CAR T-cells into the posterior fossa was able to eradicate tumor burden. Furthermore, intravenous administered single infusion of 10x 106 B7-H3 CAR T-cells succeeded in crossing the blood-brain barrier and lead to prolonged survival (p= 0,007). CONCLUSIONS: We show B7-H3 overexpression on various medulloblastoma and primary patient sample. CAR T-cell targeting B7-H3 is efficacious in eradicating medulloblastoma.