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有针对性的甘氨酸降解增强了固体瘤的细胞免疫疗法

Jicheng Wu^1,2,3, Xudong Wang^4,5, Yuqiao Huang^1,2

¹Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Proceedings of the National Academy of Sciences of the United States of America

|September 11, 2023

概括

这项研究引入了一种新的脱氧化策略,以增强固体瘤的化学抗原受体-巨细胞 (CAR-iMac) 治疗. 将脱氧化与CAR-iMac治疗结合起来,可以通过克服免疫抑制来有效地对抗瘤.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物化学生物化学

背景情况:

化学抗原受体T (CAR-T) 细胞免疫疗法在血液癌症中取得了成功,但在固体瘤中有效性有限.
固体瘤通常通过像糖免疫检查点这样的机制逃避免疫检测.

研究的目的:

开发一种策略,通过向癌细胞的sialoglycans来增强对固体瘤的CAR-iMac疗法.
研究结合癌细胞脱氧和CAR-iMac采用细胞治疗的治疗潜力.

主要方法:

设计的瘤向分子 - - 化酶结合物,以从癌细胞中去除化糖.
在小鼠模型中评估了脱氧化对CAR-iMac透,激活和抗瘤功效的影响.
调查了酸结合性免疫球蛋白类莱克丁 (Siglec) - 5和Siglec - 10检查点的作用.

主要成果:

脱增强了CAR-iMac透和激活对固体瘤的作用.
结合脱氧和CAR-iMac疗法在小鼠中显示出显著的抗瘤作用和延长生存时间.
治疗效果与对巨细胞的Siglec-5/Siglec-10检查点的封锁有关.

结论:

与CAR-iMac免疫疗法相结合的消毒提供了一种有希望的方法来治疗固体瘤.
这种策略将免疫排除的"冷瘤"转化为免疫敏感的"热瘤".
抑制葡萄糖免疫检查点为开发有效的癌症免疫疗法提供了新的途径.

关键词:

希格莱克斯 (Siglecs) 是一个符号.细胞免疫疗法细胞免疫疗法脱氧化是脱氧化的一种.酸是酸的一种.固体瘤是一种固体瘤.

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