Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor

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Abstract

Genetically modified T cells to recognize tumor-associated antigens by transgenic TCRs or chimeric antigen receptors (CAR) have been successfully applied in clinical trials. However, the disadvantages of either TCR mismatching or the requirement of a surface tumor antigen limit their wider applications in adoptive T cell therapy. A TCR-like chimeric receptor, specific for the melanoma-related gp100/HLA-A2 complex was created by joining a TCR-like antibody GPA7 with the endodomains of CD28 and CD3-ζ chain. This TCR-like CAR, GPA7-28z, was subsequently introduced into human T cells. Retargeted T cells expressing GPA7-28z could exhibit efficient cytotoxic activities against human melanoma cells in vitro in the context with HLA-A2. Furthermore, infusion of GPA7-28z-transduced T cells suppressed melanoma progression in a xenograft mouse model. Redirecting human T cells with TCR-like CARs would be a promising alternative approach to TCR-mediated therapy for melanoma patients, which is also feasible for targeting a variety of other tumor antigens.

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CITATION STYLE

APA

Zhang, G., Wang, L., Cui, H., Wang, X., Zhang, G., Ma, J., … Gao, B. (2014). Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor. Scientific Reports, 4(SREP03571). https://doi.org/10.1038/srep03571

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