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 that targets various 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 anti-
glypican 3 (GPC3)
single-chain variable fragment (scFv) 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 anti-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 cells toward
tumors, which providing a potential strategy on treatment of solid
cancer clinically.