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实体瘤细胞免疫治疗:进展、挑战与未来方向

英文原题:Cell-based immunotherapies for solid tumors: advances, challenges, and future directions.

PubMed 2025/04/28(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

研究概要

基于细胞的免疫疗法,包括 CAR-T、CAR-NK 和 TCR-T 疗法,通过提供对肿瘤细胞的精准靶向,代表了癌症治疗的变革性方法。

中文摘要

包括CAR-T、CAR-NK和TCR-T疗法在内的细胞免疫疗法,通过精准靶向肿瘤细胞,代表了癌症治疗的一种变革性方法。尽管在血液系统恶性肿瘤中取得成功,这些疗法治疗实体瘤仍面临重大挑战,包括抗原异质性、免疫抑制性肿瘤微环境、细胞浸润有限、靶外毒性以及生产规模化困难。CAR-T细胞在血癌中疗效突出,但用于实体瘤受到阻碍;CAR-NK细胞可降低移植物抗宿主病风险,但也面临类似障碍。TCR-T细胞通过靶向细胞内抗原扩大了可治疗癌症范围,但须谨慎选择抗原以避免靶外作用。TIL、NK和CIK细胞等替代疗法显示出前景,但仍需优化其持久性并克服免疫抑制屏障。生产复杂、成本高,以及确保安全性和疗效,仍是关键挑战。基因编辑、多抗原靶向、合成生物学、现货型产品和个体化医疗等未来进展有望解决这些问题并扩大细胞疗法应用。持续研究与创新对于提升安全性、疗效和规模化生产能力至关重要,最终将改善患者结局。

展开英文摘要原文

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.

论文信息

作者
Zhao T、You J、Wang C、Li B、Liu Y、Shao M、Zhao W、Zhou C
单位
Department of Oncology, Ansteel Group General Hospital, Anshan, China.China
文献类型
综述
期刊
Frontiers in oncology2025
原文标识
PubMed 40356763 · DOI 10.3389/fonc.2025.1551583