Fig. 6: Adverse effects of trogocytosis in CAR-T cell therapy.
From: Trogocytosis-mediated immune evasion in the tumor microenvironment
CAR-T cell trogocytosis disrupts CAR-T cell therapy in the following ways. a CAR-T cells acquire CAR-targeted antigens, such as CD19, BCMA, and MSLN, from leukemia, myeloma, and ovarian cancer cells, respectively, to generate target-free tumor cells. b Tumor antigen-dressed CAR-T cells are attacked by other CAR-T cells, leading to fratricidal cell death. c Prolonged exposure to tumor antigens causes CAR-T cell exhaustion. Trogocytic CAR-T cells, due to their strong antigen affinity, exhibit increased expression of exhaustion markers, such as Tim-3, TIGIT, and PD1. d To counter these adverse effects, low-affinity CD19 CAR-T cells were developed to minimize trogocytosis in the context of B-cell lymphoma. Additionally, fusing the cytoplasmic tail of CTLA-4 to the CAR reduces surface CAR levels, optimizing CAR-T cell therapeutic efficacy.
