Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor----中国科学院微生物研究所

科研成果

论文题目:	Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor
作者:	Zhang Ge, Wang Lei, Cui Honglian, Wang Xiaomin, Zhang Ganlin, Ma Juan, Han Huamin, He Wen, Wang Wei, Zhao Yunfeng, Liu Changzhen, Sun Meiyi, Gao Bin*
联系作者:	Gao Bin*
刊物名称:	Scientific reports
期:
卷:	4
页:	3571
年份:	2014
影响因子:	2.927
论文下载:	http://www.nature.com/srep/2014/140106/srep03571/full/srep03571.html
摘要:	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-zeta 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.