STRIvE-02:对复发性/反射性固体瘤患者系统管理的B7-H3化学抗原受体T细胞进行首次人体I期研究
Navin Pinto1,2, Catherine M Albert1,2, Mallory R Taylor1,2
1Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.
概括
B7-H3 CAR T 细胞对于儿科固体瘤是安全的. 响应需要高CAR T细胞扩张,但瘤微环境因素是关键因素.
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:
- B7-H3是一种免疫调节蛋白,在儿科固体瘤中经常过度表达.
- 对关键器官的有限表达使B7-H3成为免疫治疗的有吸引力的目标.
- 化学抗原受体 (CAR) T细胞疗法为向B7-H3.3提供了一种有前途的方法.
研究的目的:
- 在首次在人身上进行I期临床试验中,评估系统管理的B7-H3特异性CAR T细胞的安全性和耐受性.
- 评估B7-H3 CAR T细胞在患有复发或耐药固体瘤的儿科患者的初步疗效和剂量反应关系.
主要方法:
- 使用标准的3+3剂量升级设计,以确定B7-H3 CAR T细胞在不同剂量水平的安全性.
- 纳入了16名儿科患者 (11-24岁) 的复发/耐药固体瘤.
- 九名患者接受了剂量水平1或2的治疗,并对安全性和CAR T细胞扩张进行了监测.
主要成果:
- 在第一个输液中,在不同剂量水平中没有观察到剂量限制性毒性.
- 在外周血液中检测到CAR T细胞,其中一例CAR T细胞与瘤细胞同位.
- 一名患者在第二次输液后获得了客观的部分反应,这与增强的CAR T细胞扩张和细胞因子释放综合征有关.
结论:
- 在患有固体瘤的儿科患者中,B7-H3 CAR T 细胞通常是可以容忍的,没有观察到急性点外瘤毒性.
- 显著的CAR T细胞扩张似乎是实现客观反应所必需的.
- 主体和瘤微环境因素可能在治疗结果中发挥关键作用.
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