Genetically Modified NKT Cells to Target Viral Reservoirs

项目总结 尽管长期使用有效的病毒抑制抗逆转录病毒疗法(ART)，艾滋病毒仍持续存在 仍然是根除和治愈艾滋病毒的主要障碍。免疫治疗工具，如基因 携带嵌合抗原受体(CAR)的修饰T细胞提供了一种新的、有潜力的体内治疗方法 专门针对和杀死感染艾滋病毒的细胞。这项提议的目标是通过基因工程来对抗艾滋病毒。 Cars到不变的自然杀伤T(NKT)细胞，目的是利用Cars的免疫治疗潜力 这种独特的先天T细胞亚群以组织储存部位的HIV感染细胞为靶点。我们的具体目标是： SA#1.评价转基因猕猴NKT细胞的体外扩增、信号传递和CTL活性 含有TC特异性细胞内信号域的CD4-CAR载体(NKT-CAR)；和SA#2。 过继转导的抗HIV-NKT-CARS和对照TC-CARS在体内的生物分布和持久性 SIV感染前后的猕猴。

PROJECT SUMMARY HIV persistence despite long-term administration of potent viral-suppressive antiretroviral therapy (ART) remains a major impediment to HIV eradication and cure. Immunotherapeutic tools such as genetically modified T cells with chimeric antigen receptors (CAR) offer a new and potentially promising in vivo approach to specifically target and kill HIV-infected cells. The goal of this proposal is to genetically engineer anti-HIV CARs to invariant natural killer T (NKT) cells, with the aim of harnessing the immunotherapeutic potential of this unique innate T cell subset to target HIV-infected cells at tissue reservoir sites. Our specific aims are: SA#1. To evaluate in vitro expansion, signaling, and CTL activity of macaque NKT cells when transduced with CD4-CAR vectors containing Tc-specific intracellular signaling domains (NKT-CAR); and SA#2. To evaluate in vivo biodistribution, and persistence of adoptively transferred anti-HIV NKT-CARs and control Tc-CARs in macaques before and after SHIV infection.