针对巨细胞的装甲CAR-T细胞会重置和重编程瘤微环境,并控制转移性癌症的生长
Jaime Mateus-Tique1, Ashwitha Lakshmi1, Bhavya Singh1
1Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
针对表达FOLR2或TREM2的瘤相关巨细胞 (TAMs) 的工程T细胞重新编程了瘤微环境 (TME). 这种IL-12装甲的CAR-T疗法改善了转移性癌症的存活率,毒性最小.
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:
- 表达FOLR2或TREM2的瘤相关巨细胞 (TAMs) 在固体瘤中很普遍.
- TAMs有助于免疫抑制瘤微环境 (TME),阻碍抗瘤免疫力.
研究的目的:
- 开发新的仿真抗原受体T (CAR-T) 细胞,这些细胞被设计为向和消耗瘤前TAMs.
- 研究IL-12表达CAR-T细胞对TME重编程和增强抗癌免疫力的潜力.
主要方法:
- 开发IL-12表达的CAR-T细胞,在TAM上准FOLR2或TREM2.
- 在转移性卵巢和肺癌模型中评估CAR-T疗效.
- 使用空间转录组学对TME重建的分析.
主要成果:
- 在临床前癌症模型中,IL-12装甲抗TAM CAR-T治疗显著改善了生存率.
- 治疗在低剂量没有淋巴细胞减少的情况下显示出有效性,并显示出瘤受限活性.
- 在治疗后观察到持续的TME重塑,包括免疫刺激性巨细胞和T细胞的扩张.
结论:
- 产生IL-12的,转向骨髓细胞的CAR-T细胞代表了固体癌症治疗的有希望的策略.
- 这种方法有效地重塑了免疫抑制的TME,并促进了抗瘤免疫力.
- 一个IL-12-FAS轴被确定为CAR-T介导瘤清除的关键.
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