Novel engineered T cell therapy for solid tumors

The remarkable success of cytotoxic T cells expressing chimeric antigen receptors (CAR) for the eradication of refractory blood cancers represents one of the most promising cancer therapies. However, the lack of tumor-specific antigens, the capacity of cancer cells to alter or lose their targeted antigen, and ligand-independent tonic signaling in CAR, largely limit the efficacy of this treatment. Recently, we discovered a novel subset of CD4⁺ T cell that expresses the high-affinity receptor for IgG (FcγRI) in both mouse and human and efficiently kill tumor cells coated with antibodies. While the factors that induce these cells are currently unknown, we recapitulate their killing capacity by transducing conventional CD8⁺ T cells with FcγRI along with its signaling chain. The unique design of this genetic construct enables the integration of complex signals, which are impossible to transmit using conventional CAR designs, thus inducing more potent cytotoxic activity. Moreover, since targeting tumor cells is mediated by antibodies, this technology can be applied to treat a wide range of cancers as well as refractory cancers that lost their expressed antigen, by changing the tumor-binding antibody.