The CD64/CD28/CD3 ζ chimeric receptor reprograms T-cell metabolism and promotes T-cell persistence and immune functions while triggering antibody-independent and antibody-dependent cytotoxicity

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This paper describes the development of a chimeric receptor, CD32-CR, which fuses the human FcγRII (CD32) extracellular domain to the intracellular signaling domains of CD8α, CD28, and the ζ chain. The receptor enables T cells to recognize and kill various breast and colon cancer cell lines. Notably, CD32-CR T cells trigger potent cytotoxicity, secrete proinflammatory cytokines, and protect mice from tumor growth. RNA sequencing further revealed a 42-gene signature that predicts cancer cell sensitivity and outcomes in advanced breast cancer, with ICAM1 emerging as a key regulator of CD32-CR T cell-mediated killing.

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Photo by National Institute of Allergy and Infectious Diseases on Unsplash

Photo by National Institute of Allergy and Infectious Diseases on Unsplash