CAR T-cell Integration of Multiple Input Signals Allows for Precise Targeting of Cancer.

Chimeric antigen receptor (CAR)-mediated adoptive T-cell therapy has achieved unprecedented success in the treatment of relapsed and refractory hematologic malignancies. However, this success may be more difficult to recapitulate in the treatment of metastatic solid tumors, where the lack of costimulatory signals and cytokine support as well as the strongly inhibitory microenvironment pose a substantial challenge to unleashing the antitumor potential of CAR T cells. Furthermore, nearly all described target antigens are expressed on normal tissue. In this issue of Cancer Discovery, Sukumaran and colleagues address these challenges by engineering T cells to recognize a specific expression pattern unique to the tumor site using independent chimeric molecules that cooperatively deliver a fully functional T-cell response selectively in the tumor microenvironment. (C) 2018 AACR.