Advances in CAR-T cell therapy for malignant solid tumors.

Abstract

T cells modified by chimeric antigen receptor (CAR) have the advantage of major histocompatibility complex-independent recognition of tumor-associated antigens, so can achieve efficient response to tumor targets. Chimeric antigen receptor (CAR) T cell therapy has shown a good therapeutic effect in hematological malignancies; however, its efficacy is generally not satisfactory for solid tumors. The reasons include the lack of tumor specific antigen target on solid tumors, the uncertainty of homing ability of engineered T cells and the inhibitory immune microenvironment of tumors. In clinical trials, the targets of CAR-T cell therapy for solid tumors are mainly disialoganglioside (GD2), claudin-18 isoform 2 (CLDN18.2), mesenchymal, B7 homolog 3 (B7H3), glypican (GPC) 3 and epidermal growth factor receptor variant Ш (EGFRvШ)Ⅲ. Combination of CAR-T cells with oncolytic viruses, tyrosine kinase inhibitors, and programmed death ligand-1 monoclonal antibodies may increase its efficacy. The CAR-T cell therapy for solid tumors can be optimized through gene editing to enhance the activity of CAR-T cells, adding corresponding regulatory components to make the activation of CAR-T cells safer and more controllable, and enhancing the persistence of CAR-T cells. In this article, we review the latest advances of CAR-T cell therapy in solid tumors to provide new insights for clinical application.