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通过CAR介导的IL-10释放增加了调节性T细胞的功能:对未来临床应用的相关性

Adeel Saleem¹, Qi Peng², Ziqin Tang³

¹Imaging Therapies and Cancer Group, School of Cancer and Pharmaceutical Sciences, King's College London, London SE1 9RT, UK; Peter Gorer Department, School of Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK; Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, Netherlands.

Molecular therapy : the journal of the American Society of Gene Therapy

|February 8, 2026

概括

工程调节性T细胞 (Tregs) 在抗原接触时释放免疫抑制性IL-10,增强CAR-Treg疗法的疗效. 这种向性细胞因子释放可以提高向部位的功效,同时最大限度地减少非向性效应,从而改善治疗结果.

科学领域:

免疫学免疫学免疫学
细胞疗法细胞疗法
生物技术是生物技术.

背景情况:

调节性T细胞 (Treg) 疗法对免疫耐受性障碍有希望.
抗原特异性仿制抗原受体Tregs (CAR-Tregs) 正在为移植和自身免疫性疾病进行临床评估.

研究的目的:

为了设计人类的CAR-Tregs,在CAR参与时释放免疫抑制IL-10.
通过将抗原识别与局部免疫抑制载荷释放联系起来,增强CAR-Treg的疗效并减少副作用.

主要方法:

使用HLA-A*02 CAR和IL-10生成的人类CAR-Tregs.
与具有构成性或没有IL-10表达的工程CAR-Tregs进行比较.
评估的表型,IL-10释放,在体外抑制效应细胞,以及在人性化的异种-GvHD模型中的表现.

主要成果:

成功设计的CAR-Tregs证明了抗原特异性IL-10释放,与缺乏该模块的对照组相比释放率高2.5倍.
工程没有影响CAR-Treg表型或功能.
在体内研究表明,IL-10释放具有有益作用,优于构成性IL-10表达,从而降低了CAR-Treg的疗效.

结论:

提供了设计人类CAR-Tregs在CAR参与时释放免疫抑制细胞因子的第一个原则证明.
这种向性细胞因子释放策略增强了CAR-Treg在向部位的功效.
该方法预计将限制非目标效应,改善治疗结果.

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