Cell and Gene Therapy for HIV Cure

治愈艾滋病毒的细胞和基因疗法

• 批准号: 9191169
• 负责人: KEITH R JEROME
• 金额: $ 471.5万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-14 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9191169
• 关键词: Aftercare; Animal Model; Animals; Antiviral Agents; Award; Berlin; Binding Proteins; Biology; CCR5 gene; CD19 gene; CD4 Positive T Lymphocytes; Cell Therapy; Cells; Child; Clinical Research; Clinical Trials; Communicable Diseases; Department chair; Dependovirus; Disease remission; Dose; Engraftment; Event; Florida; Generations; Genes; Genetic; Goals; HIV; HIV Infections; HIV drug resistance; HIV therapy; HIV-1; Human; IRF3 gene; Immune; Immune response; Immunity; Immunology; Immunotherapy; Individual; Infection; Macaca; Macaca mulatta; Mediating; Methodology; Microbiology; Modeling; Patients; Phenotype; Primates; Private Sector; Production; Refractory; Relapse; Research; Research Institute; Research Personnel; Research Support; Rest; Science; T-Lymphocyte; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Transplantation; Universities; Vaccination; Vaccines; Viral; Viral reservoir; Washington; Work; base; cancer therapy; exhaustion; gene therapy; improved; killings; meetings; member; microbial; mid-career faculty; neutralizing antibody; nonhuman primate; professor; programs; simian human immunodeficiency virus; statistics; therapeutic gene; tool; trafficking; virology

PROJECT ABSTRACT/SUMMARY A major obstacle to long-term control and cure of HIV has been the persistence of HIV in reservoirs that contain latently infected, resting, and productively infected CD4+ T cells. The single example of cure of HIV has provided evidence that the search for a cure is an achievable goal. Furthermore, the mechanism of cure in this case (transplantation with CCR5-negative cells) emphasizes that cell and gene therapies represent perhaps the most promising approach to cure. Here we propose a multi-investigator program to evaluate the leading cell and gene therapy approaches to HIV cure, and to study the biology of the HIV reservoir in patients and nonhuman primates undergoing these therapies. We have assembled a team consisting of leaders in the fields of HIV, cell and gene therapies, NHP models, and clinical research. We propose 3 highly integrated Initial Research Foci in pursuit of our overall goal, and 5 Scientific Research Supports that will facilitate these projects. Initial Research Focus 1 (IRF1), HIV-Resistant Anti-HIV CAR T Cells, will be led by Dr. Lawrence Corey, Member in the Vaccine and Infectious Disease Division at Fred Hutch, and co-founder and Senior Science Advisor of our private sector partner, Juno Therapeutics; Dr. David Rawlings, Director of the Center for Immunity and Immunotherapies at Seattle Children's Research Institute; and Dr. Thor Wagner, Associate Professor at Seattle Children's Research Institute. IRF2, eCD4-Ig based therapy for HIV cure, will be led by Dr. Michael Farzan, Professor and Vice Chair, Department of Immunology and Microbial Science, The Scripps Research Institute Florida. IRF3, Genetic protection of T cells after therapeutic vaccination, will be directed by Dr. James Mullins, Professor of Microbiology, and Dr. Deborah Fuller, Associate Professor of Microbiology, at the University of Washington. We hypothesize that these cell and gene therapies offer the ideal and perhaps most promising tools with which to meet the dual goals of 1) eliminating latently-infected cells after viral reactivation, and 2) improving the host's ability to control unpredictable reactivation events from a therapeutically-reduced reservoir.

项目摘要/摘要 长期控制和治愈艾滋病毒的一个主要障碍是艾滋病毒持续存在于 含有潜伏感染、静息和生产性感染的CD4+T细胞。治愈HIV的单一例子 已经提供了证据，表明寻找治愈方法是一个可以实现的目标。此外，还探讨了其治愈机制。 这一案例(CCR5阴性细胞移植)强调细胞和基因疗法代表着 也许是最有希望治愈的方法。在这里，我们提出了一个多调查者计划来评估 领先的细胞和基因治疗方法来治愈艾滋病毒，并研究患者体内艾滋病毒蓄积物的生物学 以及接受这些疗法的非人灵长类动物。我们已经组建了一支由世界各地领导人组成的团队 艾滋病毒、细胞和基因疗法、NHP模型和临床研究等领域。我们提出了3个高度集成的方案 最初的研究重点是追求我们的总体目标，以及将促进这些目标的5项科学研究支持 项目。最初的研究重点1(IRF1)，抗艾滋病毒的抗HIV-CAR T细胞，将由劳伦斯博士领导 科里，弗雷德·哈奇公司疫苗和传染病部门成员，联合创始人兼高级 我们的私营部门合作伙伴Juno治疗公司的科学顾问；中心主任大卫·罗林斯博士 西雅图儿童研究所的免疫和免疫疗法；副研究员托尔·瓦格纳博士 西雅图儿童研究所的教授。IRF2，基于eCD4-Ig的艾滋病毒治愈疗法，将由 斯克里普斯免疫学和微生物科学系教授兼副主席Michael Farzan博士 佛罗里达研究所。治疗性疫苗接种后T细胞的遗传保护IRF3将被 由微生物学教授詹姆斯·穆林斯博士和微生物学副教授黛博拉·富勒博士指导 华盛顿大学的微生物学教授。我们假设这些细胞和基因疗法提供了 实现以下双重目标的理想工具，或许是最有前景的工具：1)消除潜伏感染 病毒重新激活后的细胞，以及2)提高宿主控制不可预测的重新激活事件的能力 一种治疗效果较差的水库。