Current Challenges and Strategies for Chimeric Antigen Receptor-T-Cell Therapy for Solid Tumors

Chimeric antigen receptor (CAR)-T-cell therapy has resulted in remarkable responses in patients with certain hematological malignancies. However, its efficacy in solid tumors is disappointing. Many factors can limit the effect of CAR-T-cell therapy on solid tumors. CAR-T-cell infiltration, survival, and persistence face numerous challenges in solid tumors. Vasculature and stromal barriers, hypoxia and high metabolism of solid tumors, tumor microenvironment immunosuppression, and high numbers of heterogeneous tumor cells all are closely related to cancer progression and immune escape. These factors usually contribute to form an environment wherein tumor cells have an advantage over CAR-T cells for survival. It is thus necessary to improve immune CAR-T-cell function in solid tumors by developing strategies to reconstruct the environment or modify the CAR-T cells. In this review, we outline major obstacles of CAR-T-cell therapy for solid tumors. We also propose strategies to overcome the above challenges and barriers against CAR-T antitumor efficacy.