Optimizing CAR-T Therapy through CRISPR technology

Cancer continues to be the leading cause of death worldwide, driving an urgent need for effective and precise therapeutic strategies. The combination of CRISPR-Cas9 gene-editing technology with chimeric antigen receptor T-cell (CAR-T) therapy has represented a breakthrough in cancer treatment. This paper offers an in-depth overview of the application of CRISPR technology in enhancing CAR-T therapy. Through targeting and disrupting genes such as TRAC and B2M in T cells, universal CAR-T cells are developed, mitigating immune rejection issues in allogeneic treatments. Epigenetic editing is utilized to modulate proto-oncogene enhancers, inhibiting tumor growth. Moreover, controllable Cas9 systems, including the Rimiducid safety switch, are employed to finely tune CAR-T activity, reducing side effects like cytokine release syndrome. Studies demonstrate that CRISPR technology has significantly improved the precision, safety, and adaptability of CAR-T therapy. However, challenges remain, such as off-target effects, insufficient delivery efficiency, and limited efficacy in treating solid tumors. Looking ahead, it will be crucial to develop high-fidelity CRISPR tools like base editors, optimize targeted delivery methods, and expand clinical trials for solid tumors. As technology advances, CRISPR-enhanced CAR-T therapy is expected to become a key component of personalized cancer treatment, providing patients with better chances of recovery.