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 采用T淋巴细胞的原理具有治疗性的HIV感染诺言 已经建立了。我们的远距离目标是设计T细胞，以便他们可以控制HIV-1 在没有Haart的情况下复制。我们公司的科学创始人开创了使用 细胞和基因治疗以治疗HIV-1，我们将使用此专业知识来更好地研究 对HIV-1感染具有抵抗力的T细胞之间的关系 在没有艺术的情况下，HIV控制HIV-1复制。我们的项目是主要整合 该U19财团的网站是项目1-3产生的最有希望的方法 并入我们设计，执行和分析的I期临床试验中。此外，我们会的 开发商业T细胞制造平台，该平台将使受艾滋病毒感染的人访问 进行嵌合抗原受体（CAR）治疗。该项目的具体目的是：1）定义 扩展T细胞进行HIV治疗研究的最佳方法：使用TMunity的T细胞扩展专业知识 和专有技术，我们将系统地讨论最好的媒体，人工APC和 制造平台以开发优化协议，以扩展具有高度功能性T细胞 用于将作为HIV治疗方案的一部分的优质植入潜力。 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 在分析治疗中断期间反弹：随着该U19成员的输入， 科学咨询委员会（SAB）和NIH计划官员，我们将计划并执行I期 使用AIM1。3）执行此新制造方案的临床试验 对AIM 2中收集的样品的相关研究，以开发可检验的假设 可以改善用于HIV感染的自适应T细胞疗法：使用从 信息时间点，我们将执行检查T细胞功能和 在没有的情况下，持久性和所选干预措施控制艾滋病毒复制的能力 艺术。