针对PD-1/PD-L1轴的基于类抑制剂:癌症的潜在免疫疗法
Magdalena Bojko1, Katarzyna Węgrzyn2, Emilia Sikorska1
1University of Gdańsk, Faculty of Chemistry, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Translational oncology
|February 15, 2024
概括
研究人员开发了一种新型的抑制剂, (L11),它针对PD-1/PD-L1免疫检查点. 这种具有作为一种非抗体癌症免疫疗法的潜力,它通过阻断癌症免疫逃逸来阻止癌症免疫逃逸.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 编程细胞死亡蛋白1 (PD-1) /编程细胞死亡连接体1 (PD-L1) 轴是免疫调节的关键抑制免疫检查点.
- 癌细胞利用PD-1/PD-L1途径进行免疫逃避,使其成为癌症免疫治疗的主要标.
- 目前的免疫疗法主要使用针对PD-1/PD-L1的抗体,这些抗体具有包括免疫相关不良事件在内的局限性.
研究的目的:
- 设计,合成和评估针对PD-1/PD-L1相互作用的基于的新型抑制剂.
- 在癌症治疗中探索用于调节PD-1/PD-L1通路的非抗体替代品.
- 确定一种具有高亲和力和对PD-1/PD-L1复合体具有抑制潜力的类化合物.
主要方法:
- 基于PD-L1结构和合成PD-1-向的体设计.
- 表面等离子体共振 (SPR) 和ELISA测试用于评估与PD-1的结合.
- 竞争性结合试验,以评估PD-L1被的取代.
- 基于细胞的测试以确定对PD-1/PD-L1复合体的抑制性质.
- 核磁共振 (NMR) 和分子动力学 (MD) 模拟以研究结构和结合方式.
主要成果:
- 一种,PD-L1 (L11),被确定为一种强大的抑制剂.
- (L11) 显示出强大的与PD-1的结合亲和力,并与PD-L1.1有效竞争.
- 细胞测试证实 (L11) 抑制PD-1/PD-L1复合体形成的能力.
- MD模拟表明 (L11) 在与PD-L1.1相同的位置与PD-1结合.
结论:
- 开发的 (L11) 有效地向并抑制PD-1/PD-L1免疫检查点.
- 基于的抑制剂为癌症免疫治疗提供了一个有希望的非抗体替代品.
- (L11) 作为一种潜在的治疗性化合物,用于对PD-1/PD-L1轴进行进一步的优化.
更多相关视频
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
1.2K
09:06Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
1.5K
相关概念视频
Tumor Immunotherapy
524
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.
524
Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
Cancer Vaccines
367
Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
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...
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...
367
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...
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...
4.9K
