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抗原特异性T细胞免疫疗法通过体内mRNA输送

Fang-Yi Su¹, Jamison C Siebart¹, Ching S Chan¹

¹The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332, USA.

bioRxiv : the preprint server for biology

|November 18, 2024

概括

研究人员开发了针对性T细胞工程的抗原呈现纳米粒子 (APN). 这种免疫疗法方法显示,通过精确修改T细胞在体内治疗自身免疫性疾病和癌症具有前途.

科学领域:

免疫学免疫学免疫学
纳米技术纳米技术
生物技术是生物技术.

背景情况:

免疫疗法为自身免疫性疾病和癌症提供了潜力,但由于广泛的T细胞调节,它面临着挑战.
目前的T细胞工程策略通常涉及复杂的ex vivo操纵.

研究的目的:

开发一种新的体内方法,利用mRNA输送工程抗原特异性T细胞.
创建抗原呈现纳米颗粒 (APN) 用于向的T细胞修饰.

主要方法:

APNs是用脂纳米粒子核心构建的,其功能与类主要基因相容性复合体 (pMHCs) 相结合.
通过同源的T细胞受体介导的内细胞突变实现了抗原特异性T细胞转染.
在1型糖尿病和多发性髓瘤的小鼠模型中评估了APN的疗效.

主要成果:

在1型糖尿病模型中,APN选择性地耗尽了自身反应性T细胞,实现了持久的血糖控制.
在多发性骨髓瘤模型中,APNs设计了具有抗癌化学抗原受体 (CARs) 的病毒特异性T细胞.
使用APNs获得的治疗结果与ex vivoCAR T细胞疗法相当.

结论:

APNs代表了体内T细胞工程的一个可行的策略.
这种方法使得针对自身免疫性疾病和癌症的抗原特异性免疫疗法成为可能.
APNs为传统的ex vivo细胞疗法提供了一个有前途的替代方案.

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