通过细胞毒性抗体-药物结合的有效载荷对瘤微环境进行免疫重编程
Srishti Chakravorty1, Yulia Zybina2, Eunseon Ahn1
1Merck & Co., United States.
Molecular cancer therapeutics
|December 2, 2025
概括
不同的抗体-药物联合体 (ADC) 独特地影响瘤微环境 (TME). 虽然T-MMAE和T-DXd都显示出抗瘤作用,但它们在TME内引起了不同的免疫细胞反应.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 抗体-药物联合体 (ADC) 是有效的癌症治疗方法,但它们对瘤微环境 (TME) 的影响尚未完全理解.
- 了解ADC诱导的TME变化对于优化癌症治疗至关重要.
研究的目的:
- 研究两种向HER2的ADCs,T-MMAE和T-DXd在TME上的不同影响.
- 为了比较不同ADC有效载荷对瘤透免疫细胞的免疫调节作用.
主要方法:
- 使用了一种表达人类HER2的免疫能力强的小鼠模型.
- 评估T-MMAE和T-DXd,评估免疫细胞透,髓状细胞表型和抗瘤反应.
- 结合ADC与抗PD-1免疫疗法.
主要成果:
- T-MMAE增加了免疫细胞的透,特别是具有特定基因表达特征的巨细胞.
- T-DXd减少了免疫细胞的透,但增强了抗原呈现细胞 (APC) 上的CD80表达.
- 这两种ADC与抗PD-1结合时,都显示出添加性抗瘤作用,并通过CD8+T细胞诱导免疫记忆.
结论:
- 不同的ADC有效载荷在TME内诱导不同的免疫反应,影响髓状细胞激活.
- 这些发现强调了考虑基于ADC的癌症治疗的有效载荷特异性TME调制的重要性.
相关概念视频
Tumor 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
Targeted 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
Cytotoxic T Cells-mediated Immune Response
6.4K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.4K
The Tumor Microenvironment
7.6K
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...
7.6K


