Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions

Chimeric antigen receptor-T (CAR-T) cell therapy has made considerable advancements in the treatment of malignant tumors; however, its clinical application continues to face challenges such as low response rates and relapse, which are critical issues requiring urgent resolution. The insufficient functionality of CAR-T cells remains a core factor affecting their clinical efficacy. This article provides a systematic review of various strategies to enhance CAR-T cell functionality, including structural modification and gene editing of chimeric antigen receptor CAR molecules, optimization of manufacturing processes, enhancement of CAR-T cells to counteract the inhibitory tumor immune microenvironment, and combination therapies with other drugs. In terms of optimizing CAR molecules, particularly the development of dual-target CARs, this approach not only effectively prevents antigen escape but also significantly enhances the activation, proliferation, and anti-tumor efficacy of CAR-T cells. Gene editing technology offers new opportunities to improve the persistence, proliferative capacity, and anti-tumor activity of CAR-T cells, thereby enhancing their function and reducing disease relapse. Furthermore, epigenetic regulation augments the adaptability of CAR-T cells, strengthening their anti-tumor effects. Simultaneously, combining CAR-T cell therapy with other immunotherapies provides fresh perspectives for improving overall treatment efficacy. However, challenges remain in areas such as the precision of gene editing, reversibility of epigenetic regulation, and optimization of CAR structures. Future research should focus on refining these strategies and exploring their synergistic applications to maximize the therapeutic potential of CAR-T cell therapy. With ongoing technological advancements, CAR-T cell therapy is poised to achieve groundbreaking applications in a broader range of malignant tumor treatments, offering new hope to patients.