一种基于共价的溶酶体向蛋白质降解平台,用于癌症免疫治疗
Youmei Xiao1, Zhuoying He1, Wanqiong Li2
1School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, Guangdong Province, China.
一个新的基于的平台 (Pep-TACs) 有效降解膜蛋白,包括PD-L1,增强抗瘤免疫力,并通过血脑屏障治疗脑瘤.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- lysosome-targeting chimeras (LYTACs) 是有效的膜蛋白降解,但面临合成和瘤透的挑战.
- 基于抗体的LYTACs在透固体瘤和穿越血脑屏障 (BBB) 的能力有限.
研究的目的:
- 开发一种基于模块化的新型向降解平台 (Pep-TACs),用于膜蛋白降解.
- 克服LYTACs在合成,瘤透和BBB交叉方面的局限性.
主要方法:
- 设计的共价化学基基向降解平台 (Pep-TACs) 具有灵活的基基组.
- 利用转移素受体 (TFRC) 介导的溶酶体向性内细胞分解来降解蛋白质.
- 评估Pep-TACs在降解PD-L1,增强T细胞功能的有效性,并在瘤模型中促进巨细胞化,包括脑瘤.
主要成果:
- -TACs显著降低了PD-L1在各种免疫细胞和瘤细胞的表达,特别是在酸性瘤微环境中.
- 证明增强的T细胞功能和巨细胞介导的瘤 fagocytosis.
- 在抗PD-1-响应型和抗PD-1-耐药型模型中实现显著的抗瘤免疫反应.
- 表明Pep-TACs可以穿越BBB,并延长脑部瘤的小鼠的存活时间.
结论:
- 引入了基于TFRC的模块化共价降解平台 (Pep-TACs) 进行高效的膜蛋白降解.
- 由于其BBB透和有效性,Pep-TACs为免疫疗法提供了一个有前途的策略,特别是在脑瘤中.
- 该平台促进了向蛋白质降解,并增强了抗瘤免疫反应.
更多相关视频
11:58Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
Published on: March 8, 2018
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
相关概念视频
Tumor Immunotherapy
Targeted Cancer Therapies
There are several types of targeted therapies against...
The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
