可变PD-1糖化调节免疫检查点抑制剂的活性
Chih-Wei Chu1, Tomislav Čaval1, Frederico Alisson-Silva1
1InterVenn Biosciences, South San Francisco, CA, USA.
Life science alliance
|January 4, 2024
概括
卡姆雷利祖马布和塞米普利马布通过其基化甘氨酸结合免疫检查点PD-1. 这种针对PD-1的特定糖化变体的向结合可能会导致更个性化的癌症疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 葡萄糖生物学 葡萄糖生物学
- 在瘤学瘤学.
背景情况:
- 免疫检查点抑制剂,如针对PD-1的单克隆抗体,在各种固体瘤中提供显著的临床益处.
- 这些抗体的疗效和毒性概况的变化可能源于它们独特的分子特性.
研究的目的:
- 为了研究卡梅利祖马布,塞米普利马布和免疫检查点PD-1之间的分子相互作用.
- 探索PD-1糖化在抗体结合中的作用及其潜在的临床影响.
主要方法:
- 利用蛋白质和细胞糖基工程技术.
- 分析了camrelizumab和cemiplimab对PD-1的结合偏好.
- 在非小细胞肺癌患者中评估了fucosylated PD-1的度.
主要成果:
- 卡姆雷利祖马布和塞米普利马布通过与其化甘氨酸的相互作用,特别是在阿斯巴拉金N58残留物上优先结合PD-1.
- 在非小细胞肺癌患者的血液中,fucosylated PD-1 的度与疾病阶段相关.
结论:
- 像PD-1这样的表面受体的葡萄糖化可以引导抗体的发展,对葡萄糖化变体具有增强的选择性.
- 这种方法可能使得产生差异化抗体并促进癌症治疗中的个性化治疗策略.
相关概念视频
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
Dipeptidyl Peptidase 4 Inhibitors
188
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
188


