双基HER2向的纳米体结合剂在耐药瘤细胞中与trastuzumab协同作用
Xinlin Liu1,2, Li Guo3, Yihuan Wang2,4
1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Frontiers in immunology
|November 12, 2025
概括
一种针对HER2 (人体表皮生长因子受体2) 的新型双型纳米体结合剂在克服对当前疗法的耐药性方面显示出有前途. 这种工程制造的药物在 HER2 阳性癌症中表现出卓越的疗效,包括对 trastuzumab 耐药的癌症.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物技术是生物技术.
背景情况:
- 人类表皮生长因子受体2 (HER2) 是各种固体瘤中关键的瘤驱动因素.
- 虽然HER2向疗法如trastuzumab和pertuzumab提供临床益处,但耐药性仍然是一个重大障碍.
- 开发下一代HER2向剂对于改善癌症治疗至关重要.
研究的目的:
- 设计和评估一种基于纳米体的新型双型结合剂,针对HER2的不同域.
- 评估这种新药在HER2表达型和逆祖祖马布耐药癌症模型中的疗效.
- 为了阐明双离子粘合剂的作用机制.
主要方法:
- 一种基于双型纳米体的结合剂 (A9F5-H2F5-Fc,AH) 的工程,针对HER2的细胞外域I和II.
- 在HER2表达瘤细胞中对受体和,内化和降解的评估.
- 评估同步抗瘤疗效在与trastuzumab结合使用的对trastuzumab耐药癌细胞.
- 结构建模以预测结合模式和HER2聚类.
主要成果:
- 工程结合剂AH表现出较高的HER2受体和,内化和降解,与trastuzumab加上pertuzumab相比.
- 在对抗瘤细胞中,AH与trastuzumab结合表现出优越的协同抗瘤疗效.
- 结构建模提出了一个独特的"跨结合模式",导致多价值HER2聚类.
结论:
- 理性设计的双型纳米体结合剂AH显示出在HER2阳性癌症中克服特鲁苏马布耐药性的潜力.
- 基于纳米体的双类策略代表了增强抗瘤疗效的有希望的方法.
- 对于HER2驱动的恶性瘤,AH提供了一个潜在的下一代治疗策略.
更多相关视频
13:59High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds
Published on: August 18, 2023
2.7K
13:19Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
3.7K
相关概念视频
02:57Targeted Cancer Therapies
8.6K
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...
8.6K
02:50Combination Therapies and Personalized Medicine
5.9K
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...
5.9K
01:27Tumor Immunotherapy
1.7K
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.
1.7K