Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor
Ge Zhang, Lei Wang, Honglian Cui, Xiaomin Wang, Ganlin Zhang, Juan Ma, Huamin Han, Wen He, Wei Wang, Yunfeng Zhao, Changzhen Liu, Meiyi Sun, Bin Gao, Ge Zhang, Lei Wang, Honglian Cui, Xiaomin Wang, Ganlin Zhang, Juan Ma, Huamin Han, Wen He, Wei Wang, Yunfeng Zhao, Changzhen Liu, Meiyi Sun, Bin Gao
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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Source: PubMed