Designing T cells to Functionally Cure HIV-1 infection

项目3：摘要 CD 4 T细胞在协调免疫应答中起着关键作用， 控制和消除病毒感染。由于HIV-1对CD 4 T细胞的嗜性， HIV-1特异性CD 4 T细胞，CD 4 T细胞对抗HIV-1感染的反应受到损害。 该项目的基本目标是开发一种策略， 活动，以打击艾滋病毒-1感染。与项目2合作，我们将雇用最多的 保护CD 4 T细胞免受HIV-1感染的有效方法。接下来，我们将研究哪种CD 4 T细胞 细胞亚群和嵌合抗原受体最好地恢复持久的HIV-1特异性活性， CD 4 T细胞。我们将与项目4密切合作，以确定控制持久性的关键因素。 和CD 4 T细胞的功能。然后利用这些信息我们将进一步完善我们的基因 工程化策略以增强抗HIV-1 CD 4 T细胞活性。在aim 3中，我们将采用 使用人源化小鼠的T细胞试验，以确定哪种工程化组合提供 最有效和持久的控制HIV-1复制。这些研究将提供基础， 将遵循项目1所述研究的临床试验的依据。 SA 1：为了鉴定最佳的CD 4 CAR共刺激结构域和细胞类型，以提供持久的免疫应答， 体外控制HIV-1感染。 SA 2：为了鉴定最佳的CD 4 CAR共刺激结构域和细胞类型， 最有助于HIV-1特异性的CD 8 T细胞。 SA 3：研究受保护的HIV-1特异性T细胞是否可以在功能上控制 体内HIV-1复制。.

PROJECT 3: ABSTRACT CD4 T cells play a key role orchestrating the immune response and play an important role controlling and eliminating viral infections. Due to HIV-1 tropism for CD4 T cells and especially HIV-1 specific CD4 T cells, the CD4 T cell response to combat HIV-1 infection is compromised. The underlying goal of this project is to develop a strategy that would restore full CD4 T cell activity to fight against HIV-1 infection. Working with Project 2, we will employ the most effective way to protect CD4 T cells from HIV-1 infection. Next, we will examine which CD4 T cell subset and which chimeric antigen receptor best restores durable HIV-1 specific activity to CD4 T cells. We will work closely with Project 4 to define the key factors that control the durably and functionality of CD4 T cells. Then using this information we will further refine our gene engineering strategy to enhance anti-HIV-1 CD4 T cell activity. In aim 3 we will model adoptive T cell trials using humanized mice to determine which combination of engineered provide the most effective and durable control of HIV-1 replication. These studies will provide the basis and rationale for a clinical trial that will follow the study described in Project 1. SA1: To identify the optimal CD4 CAR costimulatory domain and cell type to give durable control of HIV-1 infection in vitro. SA2: To identify the optimal CD4 CAR costimulatory domain and cell type that provides the most help to HIV-1 specific CD8 T cells. SA3: To investigate whether protected HIV-1 specific T cells can functionally control HIV-1 replication in vivo. .