开发LAG-3/FGL1阻断,并与放射治疗结合用于癌症免疫治疗
Yuzhen Qian1, Yixuan Sun2, Peishang Shi1
1School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
Acta pharmaceutica Sinica. B
|March 15, 2024
概括
针对免疫检查点的新型体,如淋巴细胞激活基因3 (LAG-3) 显示出作为癌症治疗的希望. 一种新的双特异性,LFOP,结合放射治疗,通过恢复T细胞功能和增加瘤透,增强抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 类治疗药物 类治疗药物
背景情况:
- 作为免疫检查点抑制剂 (ICI),类比抗体具有优势,包括更好的瘤透率和更低的成本.
- 淋巴细胞激活基因3 (LAG-3) 是一个关键的免疫检查点,在与纤维素样蛋白-1 (FGL1) 相互作用时,可能导致T细胞功能障碍.
- 与编程细胞死亡蛋白1 (PD-1) 相比,LAG-3表达在几种人类癌症中升高.
研究的目的:
- 开发针对LAG-3/FGL1相互作用的基于的新型免疫检查点抑制剂.
- 设计一种双特异性,结合LAG-3和PD-1抑制,以增强抗瘤免疫力.
- 为了评估双特异性与放射治疗结合的疗效.
主要方法:
- 菌体显示生物分析被用于识别一种 (LFP-6),该与LAG-3结合,并阻断LAG-3/FGL1相互作用.
- 酸LFP-6经过d-氨基酸修改,以创建一种耐蛋白质分解的版本 (LFP-D1).
- 通过将LFP-D1与PD-1/PD-L1阻断 (OPBP-1(8-12) 结合,构建了一个双特异性 (LFOP).
主要成果:
- 在实验室中,LFP-D1显示出恢复T细胞功能,并在体内抑制瘤生长的能力.
- 双特异性LFOP增强了T细胞的增殖和干扰素- (IFN-γ) 的产生.
- 使用LFOP和放射治疗的联合治疗显著增加了瘤中的T细胞透率,并增强了全身抗瘤免疫反应.
结论:
- 成功开发出了LAG-3/FGL1相互作用的新抑制剂,能够恢复T细胞功能.
- 设计的双特异性LFOP有效地针对LAG-3/FGL1和PD-1/PD-L1通路.
- 结合LFOP和放射治疗,为增强抗瘤免疫反应和改善癌症治疗结果提供了一个有希望的策略.
关键词:
癌症免疫疗法癌症免疫疗法FGL1 FGL1 FGL1 FGL1 FGL1 FGL1 FGL1 FGL1 FGL1 FGL1 FGL1 FGL1免疫检查站检查站现场行动组-3在PD-1中使用PD-1.在PD-L1中.这是一种类.放射疗法是一种放射治疗.更多相关视频
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