针对CD137 (4-1BB) 来提高癌症免疫治疗的安全性和疗效
Guizhong Liu1,2, Peter Luo1,2
1Adagene Inc., San Diego, CA, United States.
Frontiers in immunology
|June 19, 2023
概括
针对CD137 (4-1BB) 的激动性抗体在癌症免疫治疗中表现有前途. 本综述研究了提高抗瘤疗效的策略,同时减轻这些T细胞激活剂的毒性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- T细胞对于抗瘤免疫是至关重要的,它们的激活由抑制和共刺激受体调节.
- 目前的癌症免疫疗法主要针对抑制性受体 (例如CTLA-4,PD-1/L1).
- 开发对共刺激受体的激动性抗体 (例如CD28,CD137/4-1BB) 面临由于不良事件的挑战.
研究的目的:
- 在临床开发中审查抗CD137 (4-1BB) agonist单克隆抗体.
- 讨论CD137生物学及其对药物发现的影响.
- 为了比较在CD137向治疗中有效性与毒性脱的策略.
主要方法:
- 对抗CD137激素抗体发展的分析,重点是IgG同型.
- 与CD137连接体 (CD137L) 相对的结合性表位选择的检查.
- 在瘤微环境 (TME) 中评估Fc玛受体相互作用和条件激活机制.
主要成果:
- 不同的IgG异型会影响抗体交联和Fc玛受体的参与.
- 绑定表位和条件激活策略影响治疗潜力.
- 合理组合的CD137向剂可以增强抗瘤活性.
结论:
- 优化抗CD137主体抗体需要仔细考虑抗体设计,包括表位和同型.
- 在TME中条件激活这些抗体的策略对于安全性和有效性至关重要.
- 对合理组合的进一步研究有望改善癌症免疫治疗结果.
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