相关实验视频

Updated: May 28, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

Published on: December 7, 2019

用酶激活的直角蛋白质解剖奇米拉用于瘤微环境响应性免疫调节

Caixia Sun¹, Songhan Liu¹, Jun Wei Lau²

¹School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.

Angewandte Chemie (International ed. in English)

|February 11, 2025

概括

这项研究引入了新的酶激活可点击的PROTACs,该PROTACs降解癌症驱动蛋白质,特别是在瘤微环境 (TME) 中. 这些PROTAC可以改善药物输送,并通过降低PD-L1.1的调节来增强抗瘤免疫力.

科学领域:

生物化学生物化学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

瘤微环境 (TME) 调制对于有效的癌症治疗至关重要.
向蛋白解酶的仿真体 (PROTACs) 为向蛋白质降解提供了一种有前途的方法.
目前的PROTAC由于其复杂的结构,在选择性,合成和体内疗效方面面临挑战.

研究的目的:

开发一个新的TME响应,酶激活可点击的PROTAC系统.
克服传统PROTACs的局限性,包括选择性和瘤透.
研究这些PROTACs在癌症治疗和免疫调节中的潜力.

主要方法:

激酶激活可点击的PROTACs的设计和合成,使用标记的利多米德衍生物和标有二醇的表观遗传蛋白质配体.
瘤特异性裂变由cathepsin蛋白酶导致in situ降解剂的形成.
系统的蛋白质分析和蛋白质组分析,以评估目标降解和非目标效应.
在体外和体内对PROTAC疗效的评估,包括瘤透和PD-L1下调.

主要成果:

可点击的PROTAC显示了瘤特异性分裂和TME内表观遗传蛋白的降解.
与传统的高分子量PROTAC相比,实现了优异的瘤透.
有效下调编程死亡配体1 (PD-L1),一个关键的免疫检查点,在体外和体内.

结论:

酶激活可点击的PROTACs代表了针对性癌症治疗的新策略.
这种方法通过利用TME特定激活来提高药物输送和疗效.
开发的PROTACs显示出重塑TME和改善抗瘤免疫调节的巨大潜力.

关键词:

这就是 PROTACs.生物对角点击化学免疫调节免疫调节免疫调节目标蛋白质降解的目标蛋白质降解瘤对微环境有反应性.

更多相关视频

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

相关概念视频

The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.