期刊：Science Advances

作者列表：Huimin Shao, Fei Xu, Jiangyue Xu, Lingjie Zhou, Yao Wu, Lianjun He, Xueyi Qian, Weijie He, Nanlin Jiao, Yabin Xia, Jun Zhao, Lili Sheng, Guoliang Mao, Tao Ma, Wei Wang, Shaoxiang Luo, Li Fu, Zhenyu Xu

发表时间：2026-2-20

影响因子：12.5

DOI:10.1155/2021/3433615

主要研究成果：Abstract

Despite advances in chimeric antigen receptor T cell (CAR T cell) therapy for leukemia and lymphoma, solid tumors remain challenging because of limited target specificity and safety concerns. Neoantigens like KRASG12V, a highly prevalent yet undruggable mutation in solid tumors, offer tumor-exclusive specificity. This study developed CAR T cells targeting KRASG12V/HLA-A*02:01 using phage antibody display to identify high-affinity single-chain variable fragments. Engineered B9 CAR T cells specifically lysed tumor cells and patient-derived cancer organoids expressing KRASG12V/HLA-A*02:01, demonstrating potent antitumor activity. Animal studies showed that B9 CAR T cells effectively controlled tumor growth in subcutaneous pancreatic ductal adenocarcinoma (PDAC) xenografts, as well as in metastatic and peritoneal PDAC models. Safety assessments in NCG-HLA-A2.1 and C57BL/6 mice revealed no detectable in vivo toxicity, supporting the clinical applicability of B9 CAR T cells. Collectively, our neoantigen-targeted CAR T cell therapy against solid tumors shows great potential for future clinical trials in patients with KRASG12V/HLA-A*02:01, paving the way for clinical translation.