Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy has been proved to be an effective cancer immunotherapy strategy against haematological malignancies, but exhaustion, limited persistence, and treatment-related toxicity have been identified as major roadblocks in solid tumour treatment. Small-molecular compounds could effectively improve CAR T-cell therapy, such as preventing exhaustion, enhancing memory formation, and enhancing the antitumor activity. Additionally, adding small molecule switches based on tetracycline-controlled gene expression system is an effective strategy to improve the safety of CAR T therapy and reduce its side effects. Despite the encouraging preclinical and clinical results, challenges still remain in optimizing dosing regimens and managing drug interactions. This review aims to summarize recent advances in combined approach and to discuss the underlying mechanisms of its potential benefits.