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基于细胞支架的方法用于在固体瘤免疫治疗中宿主T细胞的现场基因工程

Hiren Y Dandia¹, Mamatha M Pillai¹, Deepak Sharma²

¹Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India.

Military Medical Research

|January 4, 2024

概括

这项研究开发了一种用于in situT细胞修饰的新型支架,有效向固体瘤. 这种局部治疗减少了瘤大小和炎症,为复杂的ex vivoT细胞治疗提供了有希望的替代方案.

科学领域:

生物材料科学生物材料科学
免疫治疗是一种免疫疗法.
在瘤学瘤学.

背景情况:

针对性T细胞疗法对血液性恶性瘤有希望,但由于可访问性和异质性,在固体瘤中面临挑战.
活体基因改造和T细胞的扩张是固体瘤治疗的耗时和昂贵的障碍.

研究的目的:

开发一种在现场局部化的T细胞编程方法,使用生物材料支架进行固体瘤治疗.
为了克服ex vivoT细胞操纵和大规模细胞培养的局限性.

主要方法:

基于聚乙烯糖醇 (PEG) 的3D支架与聚-L-氨酸 (PLL) 结合,用于病毒 (LV) 载荷.
装有LV的支架携带瘤抗原特异性T细胞受体 (TCR),并在B16-OVA黑色素瘤小鼠模型中进行了测试.

主要成果:

支架没有诱导全身炎症,并且有效地招募T细胞.
在体内,支架用OVA特定的TCR转化了宿主T细胞,导致瘤定位和显著的瘤大小减少.
转化T细胞增加,而抑制性免疫细胞在瘤内减少,伴随着抗瘤细胞因子的升高.

结论:

基于支架的治疗使得T细胞在现场编程以向固体瘤,绕过了广泛的ex vivoT细胞操纵.
这种方法提供了使用宿主细胞的现成解决方案,克服了固体瘤T细胞治疗的主要障碍.

关键词:

在 B16F10-OVA 黑色素瘤.隐形病毒隐形病毒隐形病毒聚-L-氨酸是一种聚-L-氨酸.聚乙烯甘醇二烯酸盐的聚乙烯基醇二烯酸盐.通过T细胞治疗治疗.

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