| 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: | Sci Rep |
| 期: | 4 |
| 卷: | |
| 页: | 3571 |
| 年份: | 2014 |
| 影响因子: | 2.927 |
| 论文下载: | |
| 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. |
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