Gene modification strategies for next-generation CAR T cells against solid cancers.

摘要: Immunotherapies have become the backbone of cancer treatment. Among them, chimeric antigen receptor (CAR) T cells demonstrated great success in treatment hematological malignancies. However, CAR therapy against solid tumors is less effective. Antigen targeting; an immunosuppressive tumor microenvironment (TME); and infiltration, proliferation, persistence are predominant barriers preventing extension to tumors. To circumvent these obstacles, next-generation will require more potent antitumor properties, which can be achieved by gene-editing technology. In this review, we summarize innovative strategies enhance cell function improving target identification, persistence, trafficking, overcoming suppressive TME. The construction multi-target improves recognition reduces immune escape. Enhancing proliferation optimizing costimulatory signals overexpressing cytokines. equipped with chemokines or chemokine receptors help overcome their poor homing sites. Strategies like knocking out checkpoint molecules, incorporating dominant negative receptors, switch favor depletion reversal regulators