Zhao Ting, You Jinping, Wang Congyue, Li Bo, Liu Yuhan, Shao Mingjia, Zhao Wuyang, Zhou Chuang
Department of Oncology, Ansteel Group General Hospital, Anshan, China.
Department of Medical Oncology, Anshan Cancer Hospital, Anshan, China.
Front Oncol. 2025 Apr 28;15:1551583. doi: 10.3389/fonc.2025.1551583. eCollection 2025.
Cell-based immunotherapies, including CAR-T, CAR-NK, and TCR-T therapies, represent a transformative approach to cancer treatment by offering precise targeting of tumor cells. Despite their success in hematologic malignancies, these therapies encounter significant challenges in treating solid tumors, such as antigen heterogeneity, immunosuppressive tumor microenvironments, limited cellular infiltration, off-target toxicity, and difficulties in manufacturing scalability. CAR-T cells have demonstrated exceptional efficacy in blood cancers but face obstacles in solid tumors, whereas CAR-NK cells offer reduced graft-versus-host disease but encounter similar barriers. TCR-T cells expand the range of treatable cancers by targeting intracellular antigens but require meticulous antigen selection to prevent off-target effects. Alternative therapies like TIL, NK, and CIK cells show promise but require further optimization to enhance persistence and overcome immunosuppressive barriers. Manufacturing complexity, high costs, and ensuring safety and efficacy remain critical challenges. Future advancements in gene editing, multi-antigen targeting, synthetic biology, off-the-shelf products, and personalized medicine hold the potential to address these issues and expand the use of cell-based therapies. Continued research and innovation are essential to improving safety, efficacy, and scalability, ultimately leading to better patient outcomes.
基于细胞的免疫疗法，包括嵌合抗原受体T细胞（CAR-T）、嵌合抗原受体自然杀伤细胞（CAR-NK）和肿瘤浸润淋巴细胞（TIL）疗法，通过精准靶向肿瘤细胞，代表了一种变革性的癌症治疗方法。尽管它们在血液系统恶性肿瘤治疗中取得了成功，但这些疗法在治疗实体瘤时面临重大挑战，如抗原异质性、免疫抑制性肿瘤微环境、细胞浸润受限、脱靶毒性以及生产可扩展性方面的困难。CAR-T细胞在血液癌症中已显示出卓越疗效，但在实体瘤中面临障碍，而CAR-NK细胞可降低移植物抗宿主病的发生，但也遇到类似障碍。TIL疗法通过靶向细胞内抗原扩大了可治疗癌症的范围，但需要精心选择抗原以防止脱靶效应。其他疗法如TIL、NK和细胞因子诱导的杀伤细胞（CIK）显示出前景，但需要进一步优化以提高持久性并克服免疫抑制障碍。生产复杂性、高成本以及确保安全性和有效性仍然是关键挑战。基因编辑、多抗原靶向、合成生物学、现成产品和个性化医疗等未来进展有可能解决这些问题并扩大基于细胞疗法的应用。持续的研究和创新对于提高安全性、有效性和可扩展性至关重要，最终可带来更好的患者治疗效果。
