瘤性腺病毒表达检查点抑制剂用于癌症治疗
Daoyuan Xie1, Yaomei Tian1,2, Die Hu1
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Signal transduction and targeted therapy
|November 28, 2023
概括
提供免疫检查点抑制剂 (ICI) 的工程瘤病毒 (OV) 可以克服瘤耐药性. 针对特定瘤微环境 (TME) 的量身定制的OV显示出强大的长期抗瘤免疫力和记忆力.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 病毒学 病毒学
背景情况:
- 免疫检查点抑制剂 (ICI) 由于瘤微环境 (TME) 耐药性,其疗效有限.
- 瘤病毒 (OV) 可以调节TME并增强全身抗瘤免疫力.
- 根据瘤特异性免疫格局定制疗法对于有效的癌症治疗至关重要.
研究的目的:
- 设计装备ICI的新型瘤性腺病毒 (OAds),以克服TME介导的抗性.
- 研究表达SIRPα-Fc,Siglec10-Fc和TIGIT-Fc的OAds对具有不同免疫细胞组成的瘤的疗效.
- 评估OAds与现有免疫疗法结合的潜力.
主要方法:
- 三个重组OAds的生成:OAd-SIRPα-Fc,OAd-Siglec10-Fc,以及OAd-TIGIT-Fc. 这三种OAds的生成
- 在体内评估OAD在瘤抑制和免疫反应调节中的有效性.
- 在4T1瘤模型中对抗PD-1的联合治疗进行评估.
主要成果:
- 在巨主导的瘤中,OAd-SIRPα-Fc和OAd-Siglec10-Fc显示出显著的疗效.
- 在CD8+T细胞主导的瘤中,OAd-TIGIT-Fc表现出强大的抗瘤免疫力.
- 再组合性OAds诱导炎症反应,产生长期抗瘤记忆,并提高组合治疗的疗效.
结论:
- 合理设计的表达ICI的OA可以根据特定的TME免疫场景进行精确的癌症免疫疗法.
- 工程化OV提供了一个有希望的策略,以提高ICI的疗效和克服治疗耐药性.
- 基于OV的向免疫疗法具有持久抗瘤反应和长期癌症控制的潜力.
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