Impact of engineered immune cells on viral rebound

抗逆转录病毒疗法在防止艾滋病毒复制方面是有效的，但它并不能消除所有艾滋病毒前病毒， 导致存在长期的蓄水池，在停止治疗后再次引发感染。 因此，艾滋病毒感染者被要求终身接受治疗，以防止病毒反弹。如果我们可以 控制或防止病毒反弹，我们或许能够为患者提供一段非药物缓解期，或 对艾滋病毒疾病的功能性治疗。项目2旨在确定是增强的还是遗传的 经过改造的免疫细胞可以帮助延缓或最大限度地减少病毒反弹。我们将利用尖端的人性化 小鼠模型、一种新的条形码病毒报告系统和几种抗HIV嵌合抗原受体 (CARS)实现3个目标：1)评估工程抗HIV T细胞对以下HIV反弹的影响 停止抗逆转录病毒疗法；2)评估自然杀伤细胞对停止抗逆转录病毒疗法后艾滋病毒反弹的影响；3) 确定在停止抗逆转录病毒疗法后，潜伏期的减少是否影响病毒反弹。把这些放在一起 AIMS应该能让我们更好地了解控制病毒反弹的因素，并确定基因 增强细胞免疫或操纵先天免疫反应会影响病毒反弹。如果是的话， 这可能为HIV疾病的一种新的辅助治疗方法指明方向。

Antiretroviral therapy is effective in preventing HIV replication, however it does not eliminate all HIV proviruses, resulting in the presence of long-lasting reservoirs that re-kindle infection following cessation of treatment. Thus HIV infected individuals are required to remain on therapy for life, to prevent viral rebound. If we can control or prevent viral rebound, we may be able to provide patients a drug-free remission period, or a functional cure to HIV disease. Project 2 is designed to determine whether enhanced or genetically engineered immune cells can help to delay or minimize viral rebound. We will utilize cutting edge humanized mouse models, a novel barcoded virus reporter system, and several anti-HIV chimeric antigen receptors (CARs) to accomplish 3 aims: 1) Evaluate the effects of engineered anti-HIV T cells on HIV rebound following cessation of ART; 2) Evaluate the effects of natural killer cells on HIV rebound following cessation of ART; 3) Determine if reduction of the latent reservoir influences viral rebound after cessation of ART. Together these aims should allow us to better understand factors controlling viral rebound and determine whether genetic enhancement of cellular immunity or manipulation of innate immune responses can affect viral rebound. If so, this may point the way towards a new adjunctive therapeutic approach for HIV disease.