肿瘤细胞治疗研究
英文原题：Scalable and cost-effective CAR-T exosome therapies: challenges and future directions.
Scalable and cost-effective CAR-T exosome therapies: challenges and future directions.
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CAR-T 细胞疗法彻底改变了血液系统肿瘤治疗，但在实体瘤中仍面临肿瘤浸润不足、细胞因子释放综合征（CRS）和毒性等挑战。CAR-T 细胞来源外泌体（CAR-T 外泌体）可继承CAR介导的靶向能力和细胞毒性分子（如穿孔素、颗粒酶B），同时避免CRS等问题，因此是一种有前景的替代方案。其纳米级尺寸可增强肿瘤组织穿透能力，且缺乏MHC可降低免疫原性，有利于“现货型”应用。然而，受限于传统分离方法（如超速离心[UC]）产量低、设备成本高及纯化过程不一致，规模化生产仍然困难。本综述总结CAR-T 外泌体生物学、规模化生产策略和联合疗法的近期进展，并探讨如何克服免疫抑制性肿瘤微环境（例如使用免疫检查点抑制剂和细胞因子调节）。我们还讨论其临床前景和未来方向。
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized hematological cancer treatment but faces challenges in solid tumors, including poor infiltration, cytokine release syndrome (CRS), and toxicity. CAR-T cell-derived exosomes (CAR-T exosomes) offer a promising alternative by inheriting CAR-mediated targeting and cytotoxic molecules (e. g. , perforin, granzyme B), while avoiding issues such as CRS. Their nanoscale size enhances tumor penetration, and the lack of MHC reduces immunogenicity, which supports "off-the-shelf" applications.
However, scalability remains limited by low yields from traditional isolation methods [e. g. , ultracentrifugation (UC)], costly equipment, and inconsistent purification. This review summarizes recent advances in CAR-T exosome biology, scalable production strategies, and combinatorial approaches to overcome immunosuppressive tumor microenvironments (e. g. , immune checkpoint inhibitors, cytokine modulation).
We also discuss clinical prospects and future directions.
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