2026-10-14T00:30:36Z https://www.scidb.cn/oai

10.57760/sciencedb.01995 2022-08-02T14:12:57Z

2022-08-02 Tandem incorporation of a novel DAP10 chimeric receptor T cells to overcome tumor heterogeneity doi:10.57760/sciencedb.01995 en Although chimeric antigen receptor T (CAR-T) cells have achieved remarkable successes in hematological malignancies, the efficacies of CAR-T cells against solid tumors remains unsatisfactory. Heterogeneous antigen expression is one of the obstacles on its effective elimination of solid cancer cells. DNAX-activating protein 10 (DAP10) interacts with natural killer group 2D (NKG2D), acting as an adaptor, which targeting various of malignant cells for surveillance. Here, we designed a DAP10 chimeric receptor that utilized native NKG2D on T cells to target NKG2D ligand-expressing cancer cells. We then tandemly incorporated it with glypican 3 (GPC3) scFv thus to construct a dual-antigen targeting system. T cells expressing DAP10 chimeric receptor (DAP10-T cells) displayed with an enhancement on both cytotoxicity and cytokine secretion against solid cancer cell lines, and its tandem connection with  GPC3 scFv (CAR GPC3-DAP10-T cells) exhibited a dual-antigen targeting capacity on eliminating heterogeneous cancer cells in vitro and suppressing the growth of heterogeneous cancer in vivo. Thus, this novel dual-targeting system enabled a high efficacy on killing cancer cells and extended the recognition profile of CAR-T towards tumors, which providing a potential strategy on treatment of solid cancer clinically. NKG2D; DAP10; GPC3; tumor heterogeneity Shanglin Li Ruocong Zhao Diwei Zheng Le Qin Yuanbin Cui Yao Li Zhiwu Jiang Mengjun Zhong Jingxuan Shi Ming Li Xindong Wang Zhaoyang Tang Qiting Wu Youguo Long Duo Hu Suna Wang Yao Yao Shuang Liu Li-Hua Yang Zhenfeng Zhang Qiannan Tang Pentao Liu Yangqiu Li Peng Li PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset http://www.doi.org/10.1016/j.omto.2022.06.003 Science Data Bank