肿瘤细胞治疗研究
英文原题：In vivo CAR-T for solid tumors: facing all the challenges of ex vivo CAR-T and more.
In vivo CAR-T for solid tumors: facing all the challenges of ex vivo CAR-T and more.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
in vivo CAR-T 技术的出现，作为简化细胞免疫治疗的一种手段，引发了相当大的兴奋。然而，当前的 in vivo CAR-T 平台是否真正具备在实体瘤中取得成功的条件，仍不清楚。
我们认为，CAR-T 疗法在实体瘤中的主要局限性源于生物屏障与工程学限制之间复杂的相互作用。尽管 in vivo CAR-T 平台可能简化生产制造，但递送策略本身直接影响哪些 T 细胞群体被工程化改造、CAR 表达水平与持续时间、细胞表型、持久性以及安全性。
因此，in vivo CAR-T 疗法并未消除限制 ex vivo CAR-T 疗法的生物屏障，包括迁移不良、基质排斥、抗原异质性、T 细胞功能障碍和免疫抑制性肿瘤微环境（TME）。consequently，in vivo CAR-T 疗法几乎继承了所有限制 ex vivo CAR-T 疗法的挑战，同时引入了与 CAR-T 生成、持久性和可控性相关的额外局限。
因此，在血液恶性肿瘤和自身免疫性疾病中观察到的令人鼓舞的结果，可能并不能预示在实体瘤中也能取得成功。未来的进展可能较少依赖于改进基因递送，而更多依赖于建立支持 CAR-T 在肿瘤内浸润、扩增和持久存在的机制。
The emergence of in vivo CAR-T technologies has generated considerable excitement as a means of simplifying cellular immunotherapy.
However, whether current in vivo CAR-T platforms are truly positioned to succeed in solid tumors remains unclear.
We argue that the major limitations of CAR-T therapy in solid tumors arise from a complex interplay between biological barriers and engineering constraints. Although in vivo CAR-T platforms may simplify manufacturing, the delivery strategy itself directly influences which T-cell populations are engineered, the level and duration of CAR expression, cellular phenotype, persistence, and safety.
Therefore, in vivo CAR-T therapies do not eliminate the biological barriers that restrict ex vivo CAR-T therapy, including poor trafficking, stromal exclusion, antigen heterogeneity, T-cell dysfunction, and immunosuppressive tumor microenvironment (TME). Consequently, in vivo CAR-T therapies inherit nearly all of the challenges that have restricted ex vivo CAR-T therapy while simultaneously introducing additional limitations related to CAR-T generation, persistence, and controllability.
The encouraging results observed in hematologic malignancies and autoimmune diseases may therefore not predict success in solid tumors. Future advances will likely depend less on improving gene delivery and more on establishing mechanisms that support CAR-T infiltration, expansion, and persistence within tumors.
MEMBER ACCOUNT
登录成功会直接打开下一页。
