Exploring Mechanisms of Lethal CAR-Macrophage Trogocytosis

Trogocytosis (cellular nibbling) in cancer immunotherapy holds implications in immune system responses between tumor-based cancers and engineered (CAR/monoclonal antibody) macrophages interactions. Trogocytosis lethality remains unclear as it can induce target cell death, concurrent with antigen shaving and reduced therapeutic efficacy. Using a genome-wide CRISPRi screen in HER2+ ovarian cancer cells, my mentor identified genes linked to influencing cancer cell death following trogocytosis. My focus is on identifying which screened genes, using a gene competition of control versus knockdown, affect trogocytotic lethality, specifically with its influence on cytokines or direct contact that will induce the desired cell death.