通过同时提供检查点阻塞和血栓素-1降调剂来改善癌症免疫疗法
Qingqing Xiao1, Xiaotong Li1, Chang Liu1
1School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Acta pharmaceutica Sinica. B
|September 1, 2023
概括
将天然化合物与检查点阻塞疗法结合起来,可以通过使癌细胞更容易受到免疫攻击来增强抗瘤免疫力. 这种方法有望改善癌症免疫治疗结果.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药物运输 药物运输 药物运输
背景情况:
- 检查点阻塞疗法在癌症免疫疗法中表现有前途,但由于在几个恶性瘤中效果有限,它面临着局限性.
- 癌细胞对免疫破坏的反应不佳是限制检查点疗法的成功的一个关键因素.
- 将检查点抑制剂与天然产品化学敏感剂结合起来,可能会增强抗瘤免疫反应.
研究的目的:
- 为了研究将向的迪特尔类衍生物与检查点阻塞疗法结合起来,以改善癌症免疫治疗的潜力.
- 评估使用热敏脂质体用于向瘤输送的这些药物的联合输送的有效性.
- 阐明底层机制,通过这种机制,二类衍生物增强了癌细胞对免疫攻击的敏感性.
主要方法:
- 热敏脂质体的开发和利用,用于同时输送二基衍生物和抗CTLA-4抗体.
- 在体内评估联合治疗对调控性T细胞增殖和细胞毒性T细胞透瘤中的影响.
- 机制研究,以确定二类衍生物如何影响癌细胞对免疫攻击的敏感性,重点关注THBS1和CD47相互作用.
主要成果:
- 在体内,脂质体成功地将二类衍生物和抗CTLA-4联合输送到瘤部位.
- 组合疗法显著抑制了调控性T细胞的增殖,并增强了细胞毒性T细胞的透.
- 发现二类衍生物通过降低THBS1的调节来增加癌细胞对免疫攻击的敏感性,从而破坏THBS1-CD47相互作用.
- 对于另一种检查点抗体 - - 抗PD-1 - - 也观察到二类衍生物的益处.
结论:
- 同时提供THBS1抑制剂 (diterpenoid衍生物) 和检查点阻塞疗法是增强癌症免疫疗法的有希望的策略.
- 抑制THBS1是一种新的机制,可以加强检查点治疗的疗效.
- 这种综合方法为治疗现有免疫疗法耐药的恶性瘤提供了潜在的新途径.
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