针对STING,TGF-β和PD-L1的三重向可以增强CXCL16-CXCR6信号传递,从而产生强大的抗瘤反应
Ming Yi1,2, Tianye Li3, Yinhui Gu4
1Department of Breast Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China. mingyi2022@zju.edu.cn.
Nature communications
|February 9, 2026
概括
将STING激动剂与TGF-β×PD-L1双特异抗体结合起来可以增强瘤抑制. 这种新的方法,涉及TGF-β阻断和STING激活,在临床前模型中改善了免疫反应和抗瘤活性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药物开发 药物开发
背景情况:
- 针对TGF-β和PD-L1的抗体在早期表现有希望,但在临床上遇到了挫折.
- 双特异性TGF-β×PD-L1抗体 (BsAb) 的疗效受到不充分的先天免疫激活的限制.
研究的目的:
- 研究将STING激动剂与TGF-β×PD-L1 BsAb结合起来,以增强抗瘤免疫力.
- 探索涉及TGF-β阻塞,STING激活和PD-L1抑制的协同机制.
主要方法:
- 临床前模型用于评估STING激动剂,TGF-β×PD-L1 BsAb和抗PD-L1疗法的组合.
- 研究了CXCL16-CXCR6轴在调解免疫反应中的作用.
- 开发并测试了一种针对TGF-β,PD-L1和STING的新型抗体药物联合体 (Y101S).
主要成果:
- 与标准组合相比,STING激动剂和BsAb的组合显著改善了瘤抑制.
- TGF-β阻塞增强了STING激动剂单疗效,表明TGF-β抑制了STING驱动的免疫力.
- 协同作用由CXCL16-CXCR6轴介导,促进细胞毒性T细胞的招募和功能.
结论:
- 将STING激动剂与TGF-β×PD-L1阻断相结合,为癌症免疫疗法提供了一个强有力的策略.
- CXCL16-CXCR6轴对于调解协同抗瘤效应至关重要.
- 一种三重向抗体-药物合物 (Y101S) 在临床前环境中显示出卓越的疗效和免疫调节.
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