降低PD-1的调节可以通过保持细胞记忆表型和减少疲劳来提高CAR-T细胞抗瘤效率
Wanyan Ouyang1, Shi-Wei Jin1, Nan Xu2
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Journal for immunotherapy of cancer
|April 8, 2024
概括
针对B细胞成熟抗原 (BCMA) 的工程化模拟抗原受体T细胞 (CAR-T) 在复发性或耐火性多发性骨髓瘤中显示出更好的疗效和减少疲劳. 这种新型PD-1敲击CAR-T疗法在I期临床试验中显示了85.7%的整体响应率.
科学领域:
- 免疫治疗是一种免疫疗法.
- 在瘤学瘤学.
- 细胞疗法细胞疗法
背景情况:
- 针对B细胞成熟抗原 (BCMA) 的化学抗原受体T细胞 (CAR-T) 疗法对复发性或耐火性多发性髓瘤 (RRMM) 显示出前景.
- 治疗副作用和CAR-T细胞功能障碍限制了RRMM中的当前BCMA向的CAR-T疗效.
- 需要改进CAR-T细胞设计,以提高有效性和安全性.
研究的目的:
- 设计一种新的CAR-T细胞疗法,增强抗瘤活性,并改善RRMM的安全性.
- 为了研究将一个针对PD-1的短毛RNA磁带纳入BCMA-CAR T细胞的有效性.
- 在RRMM患者的I期临床试验中评估PD-1敲击BCMA CAR-T细胞的安全性和有效性.
主要方法:
- 将针对PD-1的短毛RNA磁带纳入具有OX-40共刺激域的BCMA-CAR结构中.
- 评估PD-1敲击BCMACAR-T细胞的表面CAR表达,T细胞增殖,细胞毒性,细胞因子生产和抗原刺激后的子集.
- 进行一期临床试验,以评估工程CAR-T细胞在RRMM患者中的安全性和有效性.
主要成果:
- 与父母的BCMA CAR-T细胞相比,PD-1淘汰BCMA CAR-T细胞在体外表现出减少T细胞耗尽和增加记忆T细胞的百分比.
- 在PD-1敲击BCMA CAR-T组中观察到体内增强的抗瘤活性.
- 在一期与七名RRMM患者进行的试验中,总体应答率为85.7%,可管理的细胞因子释放综合征和无神经毒性.
结论:
- 开发的PD-1淘汰BCMA CAR-T细胞疗法为管理RRMM提供了改进的方法.
- 这项研究提出了一个独立于抗原特异性的CAR-T细胞的设计概念,增强了治疗潜力.
- 这些发现表明,有希望的替代策略可以提高多发性骨髓瘤中CAR-T细胞治疗的疗效和安全性.
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