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KRAS G12V neoantigen specific T cell receptor for adoptive T cell therapy against tumors

Nat Commun. 2023-10; 
Dan Lu, Yuan Chen, Min Jiang, Jie Wang, Yiting Li, Keke Ma, Wenqiao Sun, Xing Zheng, Jianxun Qi, Wenjing Jin, Yu Chen, Yan Chai, Catherine W H Zhang, Hao Liang, Shuguang Tan, George F Gao
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摘要

KRAS mutations are broadly recognized as promising targets for tumor therapy. T cell receptors (TCRs) can specifically recognize KRAS mutant neoantigens presented by human lymphocyte antigen (HLA) and mediate T cell responses to eliminate tumor cells. In the present study, we identify two TCRs specific for the 9-mer KRAS-G12V mutant neoantigen in the context of HLA-A*11:01. The TCR-T cells are constructed and display cytokine secretion and cytotoxicity upon co-culturing with varied tumor cells expressing the KRAS-G12V mutation. Moreover, 1-2C TCR-T cells show anti-tumor activity in preclinical models in female mice. The 9-mer KRAS-G12V mutant peptide exhibits a distinct conformation from the 9-mer wildtype pept... More

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