Wang Zhiwei, Li Peixian, Zeng Xiaoyu, Guo Jing, Zhang Cheng, Fan Zusen, Wang Zhiwei, Zhu Pingping, Chen Zhenzhen
The First Affiliated Hospital of Henan University, 475004, Kaifeng, China.
School of Life Sciences, Zhengzhou University, 100 Kexue Road, Zhengzhou, 450001, China.
Cell Death Dis. 2025 Mar 27;16(1):211. doi: 10.1038/s41419-025-07454-x.
Chimeric antigen receptor (CAR)-T-cell therapy has shown remarkable curative effects on hematological tumors, driving the exponential growth in CAR-T-related research. Although CD19-targeting CAR-T-cell therapy has displayed remarkable promise in clinical trials, many obstacles are arising that limit its therapeutic efficacy in tumor immunotherapy. The "dilemma" of CAR-T cell-based tumor therapy includes lethal cytotoxicity, restricted trafficking, limited tumor infiltration, an immunosuppressive microenvironment, immune resistance and limited potency. The solution to CAR-T-cell therapy's dilemma requires interdisciplinary strategies, including synthetic biology-based ON/OFF switch, bioinstructive scaffolds, nanomaterials, oncolytic viruses, CRISPR screening, intestinal microbiota and its metabolites. In this review, we will introduce and summarize these interdisciplinary-based innovative technologies for the next generation CAR-T-cell design and delivery to overcome the key barriers of current CAR-T cells.
嵌合抗原受体（CAR）-T细胞疗法已在血液肿瘤治疗中显示出显著疗效，推动了CAR-T相关研究的指数级增长。尽管靶向CD19的CAR-T细胞疗法在临床试验中展现出了巨大潜力，但仍出现了许多障碍，限制了其在肿瘤免疫治疗中的疗效。基于CAR-T细胞的肿瘤治疗的“困境”包括致命的细胞毒性、受限的转运、有限的肿瘤浸润、免疫抑制微环境、免疫抗性和效力有限。解决CAR-T细胞疗法困境需要跨学科策略，包括基于合成生物学的开/关开关、生物指导性支架、纳米材料、溶瘤病毒、CRISPR筛选、肠道微生物群及其代谢产物。在本综述中，我们将介绍并总结这些基于跨学科的创新技术，用于下一代CAR-T细胞的设计和递送，以克服当前CAR-T细胞的关键障碍。
