Critical factors in chimeric antigen receptor-modified t-cell (Car-t) therapy for solid tumors

Abstract

The success of chimeric antigen receptor-modified T-cell (CAR-T) therapy for B-cell lymphocyte malignancies targeting CD19 places it in a rapidly growing field in cancer immunotherapy for both hematological and solid tumors. However, the two types of tumor are quite different in the following respects. Solid tumors are characterized by complex vasculatures and matrix barriers that significantly affect T-cell functions and migration. Moreover, various immunosuppressive molecules expressed in the tumor microenvironment can impede T-cell activation, and the high metabolic rate of tumors competitively suppresses the metabolism of immune cells. All these factors will exert their influences on the development of a cancer, which is a dynamic balance between the host’s immune system and the tumor. At present, solid tumors are treated primarily by surgical resection combined with radiotherapy and chemotherapy, a treatment process that is painful and not always effective. With advantages over traditional treatments, the recently developed CAR-T immunotherapy has been applied and has shown highly promising results. Nevertheless, the complexity of solid tumors presents a great challenge to this technique. This review focuses on elucidating the factors influencing the anti-tumor effects of CAR-T in the specific tumor environment, and hence exploring feasible approaches to overcome them.