介酶体 stromal 细胞保护组合菌性和辅助依赖性腺病毒免受 humoral 免疫
Ada Irmak Özcan1, Arianexys Aquino Lόpez1,2, Alexandra N Wolff1,3
1Center for Cell Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX 77030, USA.
Molecular therapy. Methods & clinical development
|July 12, 2024
概括
介质细胞 stromal 细胞 (MSCs) 有效地将结性腺病毒传递给瘤,克服中和抗体. 这种策略通过确保病毒功能,尽管存在免疫力,提高了癌症治疗.
科学领域:
- 瘤治疗性病毒疗法
- 癌症免疫学 癌症免疫学
- 基于细胞的药物递送是以细胞为基础的.
背景情况:
- 型腺病毒的系统输送对于治疗人类恶性瘤至关重要.
- 介酶体 stromal 细胞 (MSCs) 由于瘤定位和保护性质,显示出作为癌症治疗药物的输送载体的潜力.
研究的目的:
- 评估MSCs在向瘤细胞提供临床验证的瘤和辅助体依赖性腺病毒组合 (CAdVEC) 的疗效.
- 评估腺病毒血清阳性血对CAdVEC功能的影响和MSCs的保护作用.
主要方法:
- 使用MSCs将CAdVEC传递给2D和3D培养中的瘤细胞.
- 在来自腺病毒血清阳性的供体血的存在下,评估瘤溶解和辅助体依赖性腺病毒功能.
- 在中和条件下与MSC介导传递和没有MSC介导传递的CAdVEC功能进行比较.
主要成果:
- 通过MSCs传递的瘤细胞中成功证明了瘤溶解和CAdVEC功能,即使使用了阳性血清.
- 表明CAdVEC功能在没有MSC的高稀释血清阳性血时被消除.
- 当MSC在这些条件下提供时,已确认持续的CAdVEC功能.
结论:
- MSCs提供了一个强大的体外模型,用于研究菌性和辅助性病毒传播.
- 通过MSC介导的CAdVEC的输送对全身癌症治疗有益,即使存在中和性幽默反应.
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