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

G Zhang, L Wang, H Cui, X Wang, G Zhang, J Ma… - Scientific reports, 2014 - nature.com
G Zhang, L Wang, H Cui, X Wang, G Zhang, J Ma, H Han, W He, W Wang, Y Zhao, C Liu…
Scientific reports, 2014nature.com
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 …
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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