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

临床试验引擎开发 HIV 治愈研究来测试工程 T 细胞

• 批准号: 10450653
• 负责人: CHRISTINA M COUGHLIN
• 金额: $ 33.71万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10450653
• 关键词: Address; Adoptive Transfer; Autologous; B-Cell Neoplasm; Basic Science; Biological Assay; CAR T cell therapy; CD19 gene; Cell Therapy; Cell physiology; Cellular immunotherapy; Childhood Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Clinical Trials; Clinical Trials Design; Correlative Study; Custom; Data; Disease; Disease remission; Employee; Engraftment; Enrollment; FDA approved; Goals; HIV; HIV Infections; HIV therapy; HIV-1; Healthcare; Hematologic Neoplasms; Highly Active Antiretroviral Therapy; Incentives; Individual; Industry; Infection; Infrastructure; Interruption; Intervention; Knowledge; Letters; Logistics; Malignant Neoplasms; Methods; Modality; Oncology; Outcome; Patients; Pennsylvania; Persons; Phase I Clinical Trials; Positioning Attribute; Process; Protocols documentation; Refractory; Regimen; Relapse; Resistance; Rewards; Sampling; Specificity; Structure; T cell therapy; T-Lymphocyte; Technology; Testing; Therapeutic; Time; United States National Institutes of Health; Universities; Work; adverse outcome; cell bank; chimeric antigen receptor; chimeric antigen receptor T cells; clinical center; clinical predictors; cost; design; engineered T cells; experience; gene therapy; improved; improved outcome; insight; integration site; manufacturing facility; manufacturing process; member; novel; novel therapeutics; prevent; process optimization; programs; vector; viral rebound

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.

项目4-摘要 过继转移的T淋巴细胞对HIV感染有治疗前景的原理 已经很有名气了。我们的长期目标是改造T细胞，使它们能够控制HIV-1 在没有HAART的情况下进行复制。我们公司的科学创始人已经率先使用了 细胞和基因疗法治疗HIV-1，我们将利用这一专业知识更好地研究 对HIV-1感染有抵抗力的T细胞与特异性T细胞的关系 在没有抗逆转录病毒治疗的情况下控制HIV-1的复制。我们的项目是一个主要的集成 作为项目1-3产生的最有希望的方法，该U19财团的选址将是 纳入我们设计、执行和分析的I期临床试验。此外，我们还将 开发商业T细胞制造平台，使艾滋病毒感染者能够 到嵌合抗原受体(CAR)治疗。本项目的具体目标是：1)确定 HIV治愈研究中T细胞扩增的最佳方法：利用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，和 制造平台开发优化协议，以扩展高功能T细胞 优越的植入潜力将被用作艾滋病毒治疗方案的一部分。2)设计和 实施I期临床试验以测试工程T细胞预防病毒的能力 分析处理中断期间的反弹：通过本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 使用在目标1.3)中建立的这种新制造方案的临床试验执行 对目标2中收集的样本进行相关研究，以开发可检验的假设 可以改进HIV感染的过继T细胞治疗：使用从 提供信息的时间点，我们将执行有效的分析来检查T细胞功能和 选择的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持久性和能力 艺术。