Clinical Trials Engine to Develop an HIV Cure study to test engineered T cells

项目4 -摘要 过继转移的T淋巴细胞对HIV感染具有治疗前景的原理 是公认的。我们的长期目标是设计T细胞，使它们能够控制HIV-1 在没有HAART的情况下复制。我们公司的科学创始人已经率先使用 细胞和基因疗法来治疗HIV-1，我们将利用这一专业知识来更好地研究 已经对HIV-1感染具有抗性的T细胞与对HIV-1感染具有特异性的T细胞之间的关系 在没有抗逆转录病毒治疗的情况下控制HIV-1的复制。我们的项目作为一个主要的整合 作为项目1-3产生的最有前途的方法， 纳入我们设计、执行和分析的I期临床试验。此外，我们将 开发一个商业化的T细胞制造平台，使艾滋病毒感染者能够获得 嵌合抗原受体（CAR）疗法。该项目的具体目标是：1）确定 HIV治疗研究中扩增T细胞的最佳方法：使用Tmunity的T细胞扩增专业知识 和专有技术，我们将系统地解决最好的媒体，人工APC， 制造平台，以开发优化的方案来扩增高功能性T细胞， 上级植入潜力可用作HIV治愈方案的一部分。2)设计与 实施I期临床试验，以测试工程化T细胞预防病毒感染的能力。 分析治疗中断期间的反弹：根据U19成员的输入， 科学顾问委员会（SAB）和NIH项目官员，我们将计划和执行第一阶段 使用目标1中建立的新生产方案的临床试验。3)执行 对目标2中收集的样本进行相关研究，以制定可检验的假设， 可以改善HIV感染的过继性T细胞治疗：使用从 在提供信息的时间点，我们将进行经验证的检测，检查T细胞功能， 持续性和所选干预措施在缺乏艾滋病毒复制的情况下控制艾滋病毒复制的能力。 条

Project 4 - Abstract The principle that adoptively transferred T lymphocytes have therapeutic promise for HIV infection is well established. Our long range goals are to engineer T cells so that they can control HIV-1 replication in the absence of HAART. Our companies’ scientific founders have pioneered the use of cell and gene therapy to treat HIV-1, and we will use this expertise to better study the relationship between T cells that have been rendered resistant to HIV-1 infection and specific for HIV to control of HIV-1 replication in the absence of ART. Our project serves as a main integration site for this U19 consortium as the most promising approaches generated by Projects 1-3 will be incorporated into Phase I clinical trial that we design, execute and analysis. Additionally, we will develop a commercial T cell manufacturing platform that will give HIV infected individuals access to Chimeric Antigen Receptor (CAR) therapy. The specific aims of this Project are: 1) Define the optimal method to expand T cells for HIV cure studies: Using Tmunity’s T cell expansion expertise and proprietary technology, we will systematically address the best media, artificial APC, and manufacturing platform to develop an optimized protocol to expand highly functional T cells with superior engraftment potential to be used as part of HIV cure regimens. 2) Design and implement a Phase I clinical trial to test the ability of engineered T cells to prevent viral rebound during an analytical treatment interruption: With input from the members of this U19, scientific advisory board (SAB) and NIH program officers, we will plan and execute a Phase I clinical trial that uses this new manufacturing protocol established in Aim 1. 3) Perform correlative studies on samples collected in Aim 2 to develop testable hypotheses that could improve adoptive T cell therapy for HIV infection: Using banked cells collected from informative time points, we will perform validated assays that examine T cell function and persistence and the ability of the chosen intervention to control HIV replication in the absence of ART.