用化学抗原受体设计的NK细胞延迟艾滋病毒的反弹并重塑艾滋病毒水库的组成
bioRxiv : the preprint server for biology
|February 6, 2026
概括
工程自然杀手 (NK) 细胞表达了仿真抗原受体 (CAR),向并减少了人性化小鼠的潜伏HIV储存库. 这种CAR-NK细胞疗法通过向罕见的重新激活事件,显示出对持久的艾滋病毒缓解的希望.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 基因治疗 基因治疗
背景情况:
- 持久的艾滋病毒缓解需要消除潜伏的艾滋病毒储备,尽管抗逆转录病毒治疗 (ART) 仍然存在.
- 在ART抑制过程中,未经修改的自然杀手 (NK) 细胞在清除潜在感染细胞的有效性有限.
研究的目的:
- 为了设计人类初级NK细胞与仿制抗原受体 (D1D2-CAR),以准HIV Env蛋白.
- 评估D1D2-CARNK细胞在控制人性化小鼠HIV储存库中的有效性.
主要方法:
- 工程化全基原始人类NK细胞与基于CD4的CAR向HIVEnv CD4结合部位.
- 感染了CCR5-热带HIV条形码的人性化小鼠,并给了ART.
- 在ART中断后在体外和体内评估D1D2-CARNK细胞活性,使用条形码的HIV追踪和整合部位分析.
主要成果:
- D1D2-CAR NK细胞在体外选择性地杀死感染HIV的CD4 T细胞.
- 在人性化小鼠中,CAR-NK治疗在ART中断后显著延迟病毒反弹.
- CAR-NK疗法减少了反弹HIV的多样性和器官间传播,有利于主导克隆,并在关键的基因组位置减少了前病毒.
结论:
- 工程化CAR-NK细胞可以在ART抑制期间有效地向罕见的HIV再激活事件.
- CAR-NK细胞重新塑造了艾滋病毒储存库,使其处于反弹能力较低的状态,并进行了表观遗传抑制.
- 这一策略有可能实现持久的艾滋病毒缓解.
相关概念视频
Diversity of Antigen Receptors
1.6K
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
1.6K
Immune Surveillance by NK Cells and Phagocytes
8.8K
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
8.8K
Antigen Presenting Cells
3.3K
The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
3.3K
Veins as Blood Reservoirs
8.0K
Veins, while chiefly responsible for circulating blood back to the heart, also function as storage vessels for blood. They house approximately 64 percent of the body's total blood volume, a feat made possible by their high capacitance—the inherent ability to expand and accommodate large volumes of blood, even under low pressure. The large diameter and thin walls of veins augment their distensibility, significantly more so than arteries, due to their classification as capacitance...
8.0K
Classifying Matter by Composition
90.7K
Matter: Pure Substances and Mixtures
According to its composition, the matter can be classified into two broad categories — pure substances and mixtures.
A pure substance is a form of matter that has a constant composition throughout with uniform properties. For example, any sample of sucrose has the same composition and same physical properties, such as melting point, color, and sweetness, regardless of the source from which it is isolated.
A mixture is composed of two or...
According to its composition, the matter can be classified into two broad categories — pure substances and mixtures.
A pure substance is a form of matter that has a constant composition throughout with uniform properties. For example, any sample of sucrose has the same composition and same physical properties, such as melting point, color, and sweetness, regardless of the source from which it is isolated.
A mixture is composed of two or...
90.7K
Types of Receptors: Cell Surface Receptors
27.5K
Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are...
27.5K


