Progress and Future Prospects of CRISPR Gene Editing Technology in CAR-T Cell Immunotherapy

Since its inception, chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable efficacy in relapsed and refractory hematologic malignancies. However, issues such as low response rates in solid tumors, lengthy and costly autologous product preparation, and insufficient long-term safety data have consistently limited its broader clinical application. The maturation of CRISPR/Cas9 gene editing technology has provided new tools to address these bottlenecks—by simultaneously modifying multiple targets in the T-cell genome, researchers can construct off-the-shelf allogeneic CAR-T products, knock out immune checkpoints to enhance antitumor activity, integrate safety switches to control toxicity, and even expand indications to autoimmune diseases. This article focuses on the technical approaches for optimizing CAR-T cells through gene editing. It reviews the current state of research on three strategies—the construction of universal products, enhancement of therapeutic efficacy, and improvement of safety—and, drawing on the latest clinical data from the fields of hematologic malignancies, solid tumors, and autoimmune diseases, discusses unresolved issues such as off-target effects, T-cell exhaustion, and manufacturing processes. The article also provides an outlook on cutting-edge directions, including in vivo CAR-T cells and iPSC-derived cells.