通过编码抗诱抗性IL-18的型病毒进行持久的抗瘤反应
Yan Cheng1,2,3, Yuanhui Zhao1,2, Yu Liu4,5
1State Key Laboratory of Biotechnology, Medical School, Nanjing University, Nanjing, China.
Journal for immunotherapy of cancer
|December 4, 2024
概括
通过瘤性腺病毒 (oAdDR18) 输送的工程介素-18 (IL-18) 显示了增强的抗瘤免疫力和疗效. 这种基于细胞因子的治疗,结合免疫检查点抑制剂,为癌症治疗提供了一个有前途的策略.
科学领域:
- 瘤治疗性病毒疗法
- 免疫治疗是一种免疫疗法.
- 癌症研究 癌症研究
背景情况:
- 介质素-18 (IL-18) 对于免疫细胞激活至关重要,但由于IL-18结合蛋白 (IL-18BP),其临床疗效有限.
- 开发出了抗诱IL-18 (DR18) 变种,以克服IL-18BP抑制.
- 瘤性腺病毒 (oAd) 作为一种平台,可以提供像DR18这样的治疗药物.
研究的目的:
- 评估通过oAd (oAdDR18) 提供的DR18在同基因小鼠瘤模型中的疗效.
- 将oAdDR18与重组DR18蛋白 (rDR18) 和携带野生型IL-18 (oAdwtIL-18) 的oAd进行比较.
- 评估oAdDR18在与免疫检查点抑制剂联合治疗中的潜力.
主要方法:
- 使用Ad5/3仿真纤维骨干构建oAd的搭载DR18 (oAdDR18) 的oAd.
- 通过ELISA对IL-18和IFN-γ水平的评估.
- 在各种瘤携带小鼠模型中评估抗瘤效率,包括转移和组合治疗研究.
- 在瘤微环境中通过流细胞计和免疫组织化学分析免疫细胞表型.
主要成果:
- oAdDR18保持了稳定的IL-18和IFN-γ生产,表现优于rDR18.
- 在多个模型中,oAdDR18的瘤内注射显著降低了瘤生长,有效性取决于T细胞透.
- oAdDR18对局部和远程瘤表现出优异的长期抗瘤活性,包括减少肺转移.
- 与单独治疗相比,与抗PD-1抗体的联合治疗显著增强了抗瘤作用.
结论:
- oAdDR18通过诱导强大的局部和全身免疫力以及调节瘤微环境,表现出增强的抗瘤活性.
- 这种通过解性病毒疗法进行的工程性细胞因子递送是癌症治疗的有力策略.
- 将型病毒疗法与细胞因子工程结合起来,为开发针对各种疾病的基于细胞因子的新疗法提供了一个有希望的途径.
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