CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress.

A challenge for CAR-T cell therapy is the selection of the optimal targets to minimize on-target/off-tumor toxicity. Tumor escape via antigen loss and intrinsic heterogeneity is a further hurdle. TROP2, GD2, ROR1, MUC1 and EpCAM are promising targets. Persistence and trafficking to tumor cells may be enhanced by the implementation of CARs with a chemokine receptor and/or constitutively activated interleukin receptors. Fourth-generation CARs (TRUCKs) may redirect T-cells for universal cytokine-mediated killing. Combinatorial approaches and the application of CARs to other immune cells could revert the suppressive immune environment that characterizes solid neoplasms.