卡博桑提尼布通过改善效应器功能和增强瘤免疫微环境来增强CAIX特定的CAR-T细胞对抗癌
Qihong Li1, Lin Yang2, Shuyu Li3
1Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
Biochemical and biophysical research communications
|October 5, 2024
概括
将卡博赞提尼布与碳酸无水酶IX (CAIX) 向的化学抗原受体修饰T (CAR-T) 细胞结合起来,可以协同治疗小鼠的癌. 这种方法通过调节瘤免疫微环境来增强CAR-T细胞的透和功能.
科学领域:
- 免疫治疗是一种免疫疗法.
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 化学抗原受体修饰型T细胞疗法 (CAR-T) 对血液性恶性瘤具有前景,但由于瘤免疫微环境 (TIME),在固体瘤中面临限制.
- 克服TIME的策略对于提高CAR-T细胞对固体瘤的疗效至关重要.
研究的目的:
- 为了研究将卡博桑提尼布与碳酸酶IX (CAIX) 向的CAR-T细胞用于癌治疗的协同效果.
- 阐明这种组合疗法影响瘤免疫微环境和CAR-T细胞功能的潜在机制.
主要方法:
- 利用一种涉及CAIX-CAR-T细胞和Cabozantinib的组合疗法在细胞癌的正位异种移植和皮下小鼠模型中.
- 分析了瘤透T细胞,瘤相关的巨细胞,M2两极分化,编程细胞死亡-1 (PD-1) /编程死亡-1 (PD-L1) 轴表达的变化,以及CAR-T细胞效应器功能和疲劳.
主要成果:
- 组合疗法在两种癌模型中都显示出协同效果.
- 这种治疗增加了入瘤的T细胞,并减少了与瘤相关的巨细胞和M2极化.
- 卡博桑提尼布有效地阻断了PD-1/PD-L1轴,降低了PD-L1和PD-1表达,增强了CAR-T细胞效应器功能,并减少了T细胞耗尽.
结论:
- 卡博赞提尼布与CAIX-CAR-T细胞的结合代表了一种新且有效的策略,用于增强对固体瘤的CAR-T细胞疗法,特别是癌.
- 这种方法对临床翻译在推进固体瘤治疗的CAR-T细胞疗法方面显示出显著的希望.
相关概念视频
02:57Targeted Cancer Therapies
7.5K
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...
7.5K
02:50Combination 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
02:34Inhibition of Cdk Activity
4.7K
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...
4.7K
01:27Tumor Immunotherapy
489
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.
489