用T细胞重定向免疫疗法治疗多发性骨髓瘤的抗原逃逸时间
Marios Papadimitriou1, Sungwoo Ahn2, Benjamin Diamond1
1Myeloma Division, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
bioRxiv : the preprint server for biology
|June 3, 2024
概括
在多发性骨髓瘤中,导致对仿真抗原受体T细胞 (CAR-T) 疗法的耐药性的基因组事件是在治疗期间获得的,而不是先前存在的. 早期检测对这些抗原逃逸机制的持续监测不那么重要.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 基因组学就是基因组学.
背景情况:
- 驱动抗原逃逸的基因组事件是对多发性骨髓瘤 (MM) 中的仿真抗原受体T细胞 (CAR-T) 和双特异性T细胞吸引剂 (TCE) 疗法产生抗性的关键原因.
- 目前尚不清楚这些阻力驱动事件是在治疗期间获得的还是从先前存在的克隆中选择的.
研究的目的:
- 为了确定多发性骨髓瘤中抗原逃逸机制是否是在CAR-T/TCE治疗或之前的治疗期间获得的.
- 为免疫疗法耐药性的诊断策略的开发提供信息.
主要方法:
- 在CAR-T/TCE治疗之前和之后,从11名复发性耐火MM患者的全基因组测序数据中对化疗突变特征进行了基因组树重建和分析.
- 在4名患者中使用数字PCR对抗原逃逸突变的纵向跟踪.
主要成果:
- 针对BCMA和GPRC5D的体性抗原逃生机制是在诊断后获得的,可能是在CAR-T/TCE治疗期间.
- 数字PCR跟踪显示,抗原逃生突变在治疗开始后大约1年出现,在早期的几个月中无法检测到.
- 这些发现表明,抵抗机制是获得的,而不是先前存在的.
结论:
- 在多发性骨髓瘤中,抗原逃生机制在治疗过程中获得了对CAR-T/TCE疗法的耐药性.
- 减少了治疗前诊断面板的必要性;对患有这些事件风险的患者的持续监测更为重要.
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