P10.02.A CAR-T CELL-DERIVED EXOSOMES LOADED WITH THERAPEUTIC SIRNA IS A PROMISING TECHNIQUE IN THE TREATMENT OF SUBGROUP 3 MEDULLOBLASTOMA

Abstract BACKGROUND Medulloblastoma (MB) is a life-threatening childhood tumor that occurs in the cerebellum. This tumor showed resistance against several types of immunotherapies like anti-PD1, cancer vaccines, monoclonal antibodies (mAbs), and even CAR-T cells. Subgroup 3 MB is the worst threatening subtype that poorly responds to treatment. MATERIAL AND METHODS The HLX gene, a transcription factor that regulates cell growth, is highly expressed in G3-MB and is associated with poor prognosis. The si-HLX inhibited tumor growth in vitro and in vivo and promisingly showed a long survival in the immunocompetent mouse model. We developed B7-H3-CAR-T-Exosomes that can pass brain-blood barriers (BBB), target tumor cells expressing B7-H3 protein, and deliver therapeutic si-HLX. RESULTS Preliminary results revealed that CAR-T-Exosomes can induce tumor cell death due to perforin and granzyme B contents. Promisingly, the expression of HLX was significantly inhibited in the tumor cells, and tumor cell death was enhanced. B7-H3-CAR-T-Exosomes have high safety and can induce anti-tumor response without stimulating immunotoxicity side effects like cytokine release syndrome (CRS). In this study, we are highlighting anti-B7-H3-CAR-Exosomes as a promising alternative immunotherapy in medulloblastoma, particularly G3-MB. CONCLUSION We anticipate significant inhibition of tumor growth and activation of CTL effector cells in the tumor microenvironment by intravenous injection of B7-H3-CAR-T-Exos loaded with si-HLX. This study provides a new biological approach for delivering tumor suppressor RNAs and eliciting specific anti-tumor immune responses. Indeed, anti-B7-H3-CAR-T cell exosomes offer promising safety compared to cell-based immunotherapy.