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在固体癌症中准PD-L1,其髓状细胞表达CAR类免疫受体

Kayla Myers Chen¹, Daniel Grun¹, Brian Gautier¹

¹Vita Therapeutics, Baltimore, MD, United States.

Frontiers in immunology

|May 10, 2024

概括

工程化髓状细胞表达PD-1化学抗原受体 (CAR) 类免疫受体 (CARIR) 有效地准固体瘤. 这种新型的采用细胞疗法减缓了瘤生长,并在临床前模型中改善了生存率,为PD-L1阳性癌症提供了一种有希望的方法.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞疗法细胞疗法

背景情况:

固体瘤中的髓状细胞经常促进免疫抑制性瘤微环境 (TME),阻碍癌症免疫治疗.
准编程死亡连接体1 (PD-L1),经常被癌症高调,是克服免疫逃避的关键策略.

研究的目的:

开发和评估一种使用化学抗原受体 (CAR) 类免疫受体 (CARIR) 向PD-L1.1的工程骨髓细胞疗法.
评估CARIR工程骨髓细胞在体外和在合成固体瘤小鼠模型中的疗效.

主要方法:

创造了表达一种新型PD-1 CARIR,具有细胞外PD-1和细胞内CD40/CD3ζ域的工程髓状细胞.
试验室试验包括与PD-L1+细胞共培养和细胞的评估.
活体疗效在4T1乳腺瘤同基因小鼠模型中进行了测试.

主要成果:

骨髓细胞上的CARIR表达上调了共刺激分子CD86和促炎细胞因子.
在实验室中观察到PD-L1表达癌细胞系的增强性化.
采用CARIR工程骨髓细胞的移植显著抑制了小鼠的瘤生长和延长了小鼠的生存时间.

结论:

采用PD-1 CARIR工程骨髓细胞的移植是PD-L1阳性固体癌症的一个有前途的治疗策略.
这种方法有效地重塑TME并增强抗瘤免疫力.

关键词:

在PD-1中使用PD-1.在PD-L1中.采用细胞疗法采用细胞疗法嵌合式抗原受体 (CAR) 是一种巨细胞是什么?巨细胞是什么?发酵细胞的形成发酵细胞的形成固体癌症是一种固体癌症.

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