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基于定向进化发现用于体内反原受体T细胞的配体

Tomasz M Grzywa¹, Alexandra Neeser^1,2, Ranjani Ramasubramanian^1,2

¹The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Nature biomedical engineering

|August 25, 2025

概括

研究人员开发了一种新的疫苗策略,以提高仿真抗原受体 (CAR) T细胞治疗的有效性. 这种方法增强了CAR T细胞的扩张和记忆,改善了B细胞恶性瘤的治疗.

科学领域:

免疫疗法
癌症生物学
分子工程

背景情况:

化学抗原受体 (CAR) T细胞疗法对B细胞恶性瘤具有前景.
患者的复发是由于CAR T细胞损失或不充分扩张.
目前的策略缺乏有效地在体内重新刺激CAR-T细胞的方法.

研究的目的:

开发一种可通用的方法,用于发现和优化CAR T细胞疫苗的基因.
创建一种类似疫苗的刺激剂 (amph-vax),增强CAR T细胞的功能和持久性.
在B级急性淋巴细胞白血病/淋巴瘤的临床前模型中证明这种方法的有效性.

主要方法:

酵母表面显示用于识别CD19CAR中的FMC63结体.
用定向进化来确定模原的亲和度成熟.
优化的仿真物被纳入了amph- vax配方,用于小鼠模型中的体内注射.

主要成果:

使用优化模因子的CAR- T疫苗显著增强了CD19CAR- T细胞扩张和记忆的发展.
在综合基因和人性化小鼠模型中观察到疾病进展的改善.
该策略在克服CAR T细胞损失和提高治疗结果方面被证明是有效的.

结论:

产生基因组的多功能策略使得可以创建适用于任何CAR的CAR-T细胞疫苗 (amph-vax).
这种方法提供了一种方法来提高CAR T细胞的体内功能和持续性.
这些发现为在治疗B细胞恶性瘤方面更广泛地应用CAR-T细胞增强策略铺平了道路.

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