通过ADAM17功能阻断抗体增强IL-15介导的NK细胞激活和增殖,涉及CD16A,CD137和辅助细胞
Anders W Matson1, Rob Hullsiek2, Kate J Dixon3
1Graduate Program in Comparative and Molecular Biosciences, University of Minnesota, Saint Paul, Minnesota, USA.
Journal for immunotherapy of cancer
|July 25, 2024
概括
用Medi-1抗体抑制ADAM17可增强IL-15驱动的自然杀手 (NK) 细胞的激活和增殖. 这种新的策略增强NK细胞的抗瘤活性,为癌症治疗提供治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 癌症治疗 癌症治疗
背景情况:
- 自然杀手 (NK) 细胞对于癌症免疫疗法至关重要,由瘤细胞连接体和IL-15等细胞因子激活.
- 蛋白酶ADAM17通过分裂细胞表面受体来负面调节NK细胞功能.
- 抑制ADAM17可以增强IL-15介导的NK细胞增殖,这一机制需要进一步研究.
研究的目的:
- 研究ADAM17抑制增强IL-15驱动NK细胞增殖的机制.
- 探索CD16A和CD137在调解ADAM17抑制作用中的作用.
主要方法:
- 培养的人类外周血液单核细胞 (PBMC) 或用rhIL-15和/或ADAM17功能阻断抗体 (Medi-1和变体) 丰富的NK细胞.
- 评估NK细胞增殖和表型使用流细胞计.
- 通过免疫阻塞检查CD16A信号,并使用活细胞成像测量NK细胞抗瘤活性.
主要成果:
- 阻断ADAM17的抗体Medi-1显著增强了早期NK细胞激活IL-15.
- CD16A与Medi-1的接触阻断了ADAM17的分泌,延长了NK细胞的信号传递,而没有诱导功能障碍.
- 梅迪-1和IL-15之间的协同信号在CD16A+NK细胞上调节了CD137,增加了与辅助细胞的增殖.
结论:
- CD16A和CD137调解了由Medi-1和IL-15诱导的增强NK细胞激活和增殖.
- Medi-1代表了一种新的治疗策略,以促进IL-15驱动的NK细胞增殖.
- 这种方法有可能增加癌症患者NK细胞抗瘤活性.
相关概念视频
T Cell Activation and Clonal Selection
694
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
694
Cytotoxic T Cells-mediated Immune Response
883
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...
883
Immune Response Against Viral Pathogens
768
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
768
T Cell Types and Functions
986
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
986


