用于癌症免疫治疗的小分子抑制剂和相关生物标志物 - 目前的状态
Lisa Schlicher1, Luke G Green2, Andrea Romagnani1
1Cancer Cell Targeted Therapy, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.
Frontiers in immunology
|November 29, 2023
概括
小分子正在成为癌症免疫疗法的新策略,准细胞内调节剂以增强抗瘤免疫反应. 这些新药候选药物处于早期开发阶段,正在探索潜在的生物标志物.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 癌症免疫疗法已经成功地使用了针对免疫检查点的大分子.
- 小分子提供了一种新的方法,通过准抗瘤免疫的细胞内负调节剂.
- 这些调节剂存在于适应性和先天性免疫细胞,以及瘤微环境中.
研究的目的:
- 审查癌症免疫治疗中有希望的小分子候选药物的状态.
- 讨论这些疗法相关生物标志物的潜力.
- 要突出针对细胞内免疫调节的小分子的发展.
主要方法:
- 对小分子抑制剂的临床前和临床数据的审查.
- 识别免疫信号通路中的关键细胞内点.
- 对针对T细胞受体信号,共受体信号,细胞因子信号,cGAS/STING通路,腺素信号和前列腺素E信号的候选药物的分析.
主要成果:
- 一些针对T细胞信号传递的负调节剂的小分子抑制剂 (例如MAP4K1,CBL-B,PTPN2) 正处于早期临床试验阶段.
- ENPP1和TREX1的抑制剂正在临床开发中,以增强先天的抗瘤免疫力.
- 目前正在研究CD39/CD73抑制剂和EP2/EP4抗体,以抵消免疫抑制信号.
- 大多数候选人都处于发展的早期阶段.
结论:
- 小分子在癌症免疫治疗中代表了一个有前途的前沿,准各种细胞内机制.
- 进一步开发和生物标志物识别对于这些新型药物的成功至关重要.
- 这些疗法旨在通过直接调节细胞和瘤微环境中的免疫反应来克服当前免疫疗法的局限性.
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