Immunotherapy with Autologous HIV-Loaded Dendritic Cells

使用携带 HIV 的自体树突状细胞进行免疫治疗

• 批准号: 8091773
• 负责人: CHARLES R RINALDO
• 金额: $ 3.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-02 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8091773
• 关键词: Autologous; Dendritic Cells; Immunotherapy

Control of HIV-1 infection in chronically infected patients has been revolutionized by highly active antiretrovirai therapy (HAART). However, long term HAART is toxic and there is incomplete recovery of anti-HIV-1 T cell function; removal of HAART usually also results in rapid increases in viral load. Thus, we postulate that immunotherapy specifically directed to autologous virus can lead to adequate control of residual HIV-1 infection during HAART. We hypothesize that dendritic cells (DCs) loaded with apoptotic, autologous cells that are infected with autologous HIV-1 can serve as potent immunogens for activation of both CD8* and CD4 ¿ T cells specific for a broad range of autologous HIV-1 antigens. This is based on our recent findings that DCs loaded with HIV-1 infected, apoptotic cells induce CD8* and CD4* T cell responses specific for HIV-1 in vitro. To further refine this model, we propose to expand our preclinical studies by comparing the immunogenicity and the breadth of antigen specificity induced ex vivo by DCs loaded with apoptotic cells infected with autologous HIV-land DCs matured by different cytokine milieus. We will use this ex vivo model for determining the safety and immunogenicity of ex vivo loaded, autologous DCs as an HIV-1 immunogen in HIV-1 infected adults on HAART in a phase I clinical trial. Finally, we propose to monitor the breadth of CD8 ¿ and CD4 ¿ T cell responses to autologous HIV-1 and characterize viral evolutionary changes before and after ex vivo immunization. This DC-apoptotic cell model may be an ideal immunogen in that it contains all forms of HIV-1 proteins and can be used as a vehicle for therapeutic immunization with autologous virus.

慢性感染患者对HIV-1感染的控制已被高度活跃彻底改变 抗逆转录病治疗（HAART）。但是，长期HAART有毒，恢复不完全 抗HIV-1 T细胞功能；去除HAART通常还会导致病毒负荷迅速增加。那， 我们假设专门针对自体病毒的免疫疗法可导致足够的控制 HAART期间残留的HIV-1感染。我们假设装有的树突状细胞（DC） 被自体HIV-1感染的凋亡，自体细胞可以用作潜在的免疫原子 为了激活CD8*和CD4»对广泛自体HIV-1抗原的T细胞。 这是基于我们最近的发现，即DC在感染HIV-1的DC诱导CD8*。 和CD4* T细胞反应在体外特有的HIV-1。为了进一步完善该模型，我们建议 通过比较抗原特异性的免疫原性和广度来扩大我们的临床前研究 由DCS诱导的离体，该DC装有凋亡细胞，这些细胞感染了自体HIV-Land DC的成熟 不同的细胞因子环境。我们将使用该离体模型来确定安全性和免疫原性 在HIV-1感染HAART的HIV-1感染的HIV-1免疫原中的自体DC作为HAART中的HIV-1免疫原 I期临床试验。最后，我们建议监测CD8€和CD4»T细胞对的广度 自体HIV-1并表征了体内免疫之前和之后的病毒进化变化。 这种DC凋亡细胞模型可能是理想的免疫原，因为它包含所有形式的HIV-1蛋白 并可以用作自体病毒热免疫抑制的载体。