通过使用系统性TNF阻断,可以减少局部性瘤性病毒疗法的IL-12中介毒性
Miriam Valenzuela-Cardenas1, Carrie Fisher2, Mee Y Bartee1
1Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Molecular therapy. Oncology
|September 18, 2024
概括
再组合性型病毒为癌症治疗提供细胞因子,但系统性毒性仍然存在. 这些毒性,由瘤亡因子α介导,可以使用FDA批准的瘤亡因子抑制剂来减少.
科学领域:
- 瘤治疗性病毒疗法
- 免疫治疗是一种免疫疗法.
- 癌症治疗 治疗 癌症治疗
背景情况:
- 细胞因子治疗可以改善癌症的结果,但会导致严重的毒性.
- 再组合性瘤病毒向瘤输送细胞因子,提高疗效并减少副作用.
- 一种vPD1/IL-12菌瘤病毒有效回归扩散的癌症.
研究的目的:
- 调查与vPD1/IL-12相关的全身毒性机制.
- 确定在癌症患者中减轻这些毒性的策略.
主要方法:
- 用双重重组合瘤菌瘤病毒 (vPD1/IL-12) 治疗扩散性癌症.
- 转基因生物分布和系统毒性的分析.
- 研究细胞因子介导的毒性途径,包括干扰素-γ和瘤坏死因子α (TNF-α).
- 评估TNF抑制剂对毒性减轻的作用.
主要成果:
- 尽管局部转基因表达,vPD1/IL-12治疗导致了全身毒性.
- 毒性独立于干扰素-γ.
- 系统性毒性是由TNF-α与血液细胞上的TNF受体2相互作用的介导.
- 美国食品和药物管理局批准的TNF阻断剂Etanercept减轻了vPD1/IL-12介导的毒性.
结论:
- 来自型病毒的系统IL-12毒性可以独立于干扰素-γ.
- TNF-α和TNF受体2在造血细胞中调解这些毒性.
- 阻断TNF提供了一种可行的策略来管理型病毒诱导的毒性,提高临床适用性.
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