多重体免疫疗法复合物激活自然杀手细胞以治愈HIV-1病毒
Rafaëla Schober1, Bianca Brandus1, Thessa Laeremans2
1Department of Infection and Immunity, Luxembourg Institute of Health, 29, Rue Henri Koch, L-4354, Esch-Sur-Alzette, Luxembourg.
Journal of translational medicine
|November 7, 2023
概括
自然杀手激活多重体免疫疗法复合体 (NaMiX) 通过增强NK细胞对感染细胞的活性,显示出对治愈HIV-1的希望. 这种新型免疫疗法针对检查点抑制剂,增强免疫系统.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 治疗方法 治疗方法
背景情况:
- 联合抗逆转录病毒疗法 (cART) 可以控制HIV-1,但不能消除病毒储存库.
- 艾滋病毒-1感染减少了细胞毒性自然杀手 (NK) 细胞,这些细胞表达检查点抑制剂,如NKG2A和KIR2DL.
- 表达CXCR5的NK细胞对于控制HIV-1复制至关重要.
研究的目的:
- 设计和评估自然杀手激活多重体免疫治疗复合体 (NaMiX) 用于杀死感染HIV-1的细胞.
- 评估NaMiX在体外和人性化小鼠模型中的疗效.
- 研究NaMiX作为HIV-1治愈的支持策略的潜力.
主要方法:
- 通过将IL-15/IL-15Rα多元体与抗NKG2A或抗KIR单链碎片变量 (scFv) 结合而开发的NaMiX.
- 纳米X实体被多元化成六合体 (α) 或二合体 (β) 形式.
- 评估了体外模型和人性化的NSG tg-huIL-15小鼠.
主要成果:
- NaMiX增强了NK和CD8+T细胞的细胞分解活性,脱粒化和对HIV-1感染细胞的细胞因子释放.
- 反NKG2A的NaMiX表现出比抗KIR的NaMiX更强大的效果.
- 在HIV-1阳性个体中,抗NKG2ANaMiX增强了NK细胞激活,细胞毒性,IFN-γ产生和CXCR5表达.
- 在人性化小鼠中,抗NKG2A.α NaMiX改善了NK细胞功能,并减少了病毒DNA.
结论:
- 纳米X,特别是抗NKG2A.α,增强NK细胞介导的杀死HIV-1感染细胞.
- 这种方法显示了支持HIV-1治愈策略的潜力.
- NaMiX代表了HIV-1治疗的有前途的免疫疗法.
相关概念视频
01:27Cytotoxic T Cells-mediated Immune Response
928
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...
928
01:29Immune Response Against Viral Pathogens
795
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...
795
01:27Tumor Immunotherapy
533
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.
533