基于aptamer的逻辑计算对活细胞的反应,以实现非抗体免疫检查点阻塞疗法
Yu Yang1,2, Jun Xu3, Yang Sun1
1Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Journal of the American Chemical Society
|May 24, 2021
概括
这项研究引入了基于aptamer的逻辑系统,用于精确的癌症免疫治疗. 这种方法将免疫检查点抑制剂联合于癌细胞,增强T细胞反应并改善小鼠的存活率.
科学领域:
- 生物技术
- 免疫学
- 癌症研究
背景情况:
- 免疫检查点阻塞 (ICB) 治疗在实现高客观反应率和持久有效性方面面临挑战.
- 目前的ICB疗法通常依赖于抗体,因此需要开发持续治疗的替代策略.
研究的目的:
- 开发一个基于aptamer的逻辑计算系统,用于精确和持续的ICB治疗.
- 在不使用抗体的情况下,实现对抗免疫检查点的合.
主要方法:
- 细胞表面糖蛋白的代谢标记用亚胺作为化学受体.
- 使用亚化物和环氧化物之间的生物直角点击化学反应进行合.
- 实施DNA逻辑计算算法以控制基于布尔逻辑输入 (PD-L1表达和化物存在) 的aptamer结合.
主要成果:
- 通过逻辑关闭的生物对角反应成功对抗PD-L1的细胞.
- 证明了阿普坦结合引发了精确且持续的T细胞介导的抗瘤免疫疗法.
- 用这种新方法治疗小鼠的总生存时间显著延长.
结论:
- 通过DNA逻辑计算介导的生物对角反应为ICB疗法提供了一个精确而强大的平台.
- 这种基于aptamer的策略有可能提高癌症治疗的客观反应率.
- 该方法为向癌症免疫治疗提供了一种新的无抗体方法.
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