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目前对CAR T细胞相关毒性的理解和管理
Jennifer N Brudno1, James N Kochenderfer2
1Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. jennifer.brudno@nih.gov.
Nature reviews. Clinical oncology
|May 20, 2024
概括
化学抗原受体 (CAR) T细胞疗法显示出前景,但导致诸如细胞因子释放综合征 (CRS) 和神经毒性等毒性. 改进的管理策略对于患者安全和推进这种创新的癌症治疗至关重要.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 细胞疗法细胞疗法
背景情况:
- 化学抗原受体 (CAR) T细胞疗法已经改变了血液癌症的治疗方法,并正在研究固体瘤.
- 早期的CAR T细胞疗法 (2017年以来获得批准) 呈现出显著的毒性,包括细胞因子释放综合征 (CRS) 和免疫效应细胞相关的神经毒性综合征 (ICANS).
- 支持性护理和免疫抑制治疗的进步提高了CAR T细胞治疗的安全性和可行性.
研究的目的:
- 审查与CAR T细胞治疗相关的毒性的不断发展的理解和临床管理.
- 突出新发现的毒性及其管理方面的挑战.
- 强调需要在毒性管理和CAR T细胞产品开发方面进行持续研究.
主要方法:
- 临床经验的文献综述和关于CAR T细胞治疗相关毒性的已发表数据.
- 对已知和新出现的不良事件的分析,包括CRS,ICANS,运动障碍,血液毒性 (ICAHT) 和血细胞淋巴细胞样性综合征 (IEC-HS).
- 讨论当前用于毒性管理的药物治疗方法,以及缺乏通用治疗算法.
主要成果:
- 卡尔-T细胞疗法与众所周知的毒性 (CRS,ICANS) 和较少定义的毒性 (如运动障碍,ICAHT和IEC-HS) 有关.
- 持续的CAR-T细胞诱导的B细胞无形成导致低血和感染风险增加.
- 多种药物疗法用于毒性管理,但缺乏标准化的协议.
- 针对新抗原的CAR T细胞产品的开发可能会引入新的毒性,原因是对非恶性组织的非向作用.
结论:
- 有效管理与CAR T细胞相关的毒性对于成功的临床应用至关重要.
- 对毒性管理策略的持续前性评估至关重要.
- 开发少毒的CAR T细胞产品是未来研究和临床成功的关键领域.
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