针对复发性或耐药性B细胞恶性瘤的全基性现成CAR T细胞疗法
Sanam Shahid1, Susan E Prockop2, Georgia C Flynn1
1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood advances
|February 5, 2025
概括
使用爱斯坦-巴尔病毒特异性T细胞 (EBV-VSTs) 的全源"现成"仿真抗原受体 (CAR) T细胞疗法,在复发/耐药B细胞恶性瘤患者中证明了安全性和可行性. 这种CAR EBV-VST产品显示出有利的整体存活率,为患者特异性的CAR T细胞治疗提供了一个有前途的替代方案.
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:
- 化学抗原受体 (CAR) T细胞疗法提供临床益处,但受到患者特定制造的限制.
- 全基性或"现成"的CAR T细胞产品可以克服制造障碍并扩大治疗可访问性.
研究的目的:
- 评估来自爱斯坦-巴尔病毒特异性T细胞 (EBV-VSTs) 的全基CAR T细胞产品的安全性和可行性.
- 确定在患有复发性/耐药性 (R/R) B 细胞恶性瘤的患者中,CAR EBV-VST 产品多次输注的最佳剂量.
主要方法:
- 开发一种全基"现成"CAR T细胞产品,使用EBV-VSTs与一种CD19特异性CAR (19-28z) 进行基因改造.
- 16名患有R/R B细胞恶性瘤的患者根据先前的造血细胞移植 (HCT) 状态分为三组治疗队伍.
- 进行多次CAR EBV-VST输液,并将剂量优化为3 × 10^6 T细胞/kg.
主要成果:
- 没有观察到严重的细胞因子释放综合征或神经毒性;没有确定剂量限制性毒性.
- 大多数患者 (12/16) 接受了多次剂量,确定3 × 10^6 T细胞/kg为最佳剂量.
- 12个月的总生存率为81%,36个月的总生存率为75%,注射后扩张和持续性有限.
结论:
- 全基性"现成"CAR EBV-VST产品对于治疗CD19+ R/R B细胞恶性瘤是可行的和安全的.
- 这项研究支持这种方法为患者提供有利结果的潜力,克服了自主CAR T细胞疗法的局限性.
- 对优化CAR EBV-VST扩散和持久性的进一步研究可能会提高治疗疗效.
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