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先进治疗药物的临床毒性

Fraser J H Henderson¹, Simon L Hill²

¹Clinical Pharmacology and Therapeutics, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

British journal of clinical pharmacology

|June 13, 2025

概括

先进治疗药物 (ATMP) 是有前途的,但具有独特的毒性风险. 本综述详细介绍了ATMP毒性机制和管理策略,以实现更安全的临床使用.

科学领域:

*再生医学和生物技术
* 药理学与毒理学药理学与毒理学

背景情况:

*先进疗法药物 (ATMP) 提供了使用基因,组织或细胞治疗各种疾病的新疗法.
*ATMPs存在明显的安全挑战,包括免疫性,脱效应和器官特异性毒性,与传统疗法不同.
*了解和管理这些毒性对于临床转化至关重要.

研究的目的:

* 审查目前关于先进治疗药物 (ATMP) 毒性的临床证据.
* 确定ATMP相关毒性的关键机制.
*描述风险管理策略,以减轻这些不良影响.

主要方法:

*对MEDLINE和Embase数据库进行了范围审查.
*确定了报告基因疗法药物 (GTMPs),体细胞疗法,组织工程产品和组合ATMPs毒性的研究.
* 对急性和慢性临床毒性的数据进行了定性提取和整理.

主要成果:

* GTMPs,特别是CAR T细胞疗法,经常表现出急性毒性,如细胞因子释放综合征和神经毒性.
* GTMPs的慢性风险包括基因毒性和瘤性,特别是在高剂量的基于AAV的疗法中.
*体细胞疗法有免疫毒性和瘤形成的风险;组织工程产品面临生物相容性和整合性挑战.
*管理策略包括预先调节,更安全的载体设计,免疫抑制 (例如,托西利祖马布) 和长期监测.

结论:

*ATMP具有显著的治疗潜力,但需要严格的安全评估和积极的风险管理.
*解决复杂的毒性概况需要个性化的方法,先进的临床前模型和严格的监管监督.
*确保患者安全对于实现ATMPs的全部潜力至关重要.

关键词:

先进疗法的药物,先进疗法的药物.综合先进疗法的药物.细胞因子释放综合征细胞因子释放综合征基因疗法药品基因疗法药品身体细胞疗法药品药品组织工程产品是组织工程产品.毒性的毒性毒性的毒性

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