Cell and Gene Therapy for HIV Cure

项目摘要/总结 长期控制和治愈艾滋病毒的一个主要障碍是艾滋病毒在宿主中的持续存在， 含有潜伏感染、静止和生产性感染的CD 4 + T细胞。治愈艾滋病的唯一例子 已经提供了证据，证明寻找治愈方法是一个可以实现的目标。此外，治疗机制， 这种情况下（移植CCR 5阴性细胞）强调细胞和基因疗法代表， 也许是最有希望的治疗方法。在这里，我们提出了一个多调查员计划，以评估 领先的细胞和基因治疗方法来治愈艾滋病毒，并研究艾滋病毒储存在患者的生物学 和非人类灵长类动物接受这些治疗。我们已经召集了一个团队， 艾滋病毒、细胞和基因疗法、NHP模型和临床研究领域。我们建议3个高度集成的 初步研究重点，以追求我们的总体目标，和5个科学研究支持，将促进这些 项目初始研究重点1（IRF 1），抗HIV CAR T细胞，将由劳伦斯博士领导 Corey，Fred Hutch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 Therapeutics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;和Thor瓦格纳博士，助理 西雅图儿童研究所教授。IRF 2，基于eCD 4-IG的HIV治愈疗法，将由 博士Michael Farzan，教授兼副主席，免疫学和微生物科学系，斯克里普斯 佛罗里达研究所。IRF 3，治疗性疫苗接种后T细胞的遗传保护， 由微生物学教授James Mullins博士和副教授Deborah Fuller博士指导。 微生物学，在华盛顿大学。我们假设这些细胞和基因疗法提供了 理想的，也许是最有前途的工具，以满足双重目标：1）消除潜伏感染， 病毒再激活后的细胞，以及2）提高宿主控制不可预测的再激活事件的能力， 一种治疗性减少的储库。

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.