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Cell and Gene Therapy for HIV Cure

治愈艾滋病毒的细胞和基因疗法

基本信息

批准号：
10593375
负责人：
KEITH R JEROME
金额：
$ 40.73万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-14 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10593375
关键词：
Cell Gene Therapy HIV Cure

项目摘要

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/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储存库中的持续存在，含有潜伏感染、休眠和有效感染的 CD4+ T 细胞。治愈艾滋病毒的唯一例子提供的证据表明寻找治疗方法是可以实现的目标。此外，治愈机制这个案例（CCR5阴性细胞移植）强调细胞和基因疗法代表也许是最有希望的治愈方法。在这里，我们提出了一个多研究者计划来评估领先的细胞和基因治疗方法可治愈艾滋病毒，并研究患者体内艾滋病毒储存库的生物学和非人类灵长类动物接受这些疗法。我们组建了一支由各领域领导者组成的团队 HIV、细胞和基因疗法、NHP 模型和临床研究领域。我们提出3种高度集成的方案追求我们总体目标的初始研究重点，以及促进这些目标的 5 项科学研究支持项目。初始研究重点 1 (IRF1)，抗 HIV 抗 HIV CAR T 细胞，将由 Lawrence 博士领导 Corey，Fred Hutch 疫苗和传染病部门成员、联合创始人兼高级人员我们的私营部门合作伙伴 Juno Therapeutics 的科学顾问； David Rawlings 博士，中心主任西雅图儿童研究所免疫和免疫治疗；托尔·瓦格纳 (Thor Wagner) 博士，副教授西雅图儿童研究所教授。 IRF2，一种基于 eCD4-Ig 的 HIV 治愈疗法，将由 Michael Farzan 博士，斯克里普斯免疫学和微生物科学系教授兼副主席佛罗里达研究所。 IRF3，治疗性疫苗接种后 T 细胞的遗传保护，将被由微生物学教授 James Mullins 博士和副教授 Deborah Fuller 博士指导华盛顿大学微生物学。我们假设这些细胞和基因疗法提供了理想且也许是最有前途的工具，可用于实现以下双重目标：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治疗性减少的储库。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

自体干细胞移植会破坏猿猴/人类免疫缺陷病毒病毒血症反弹期间的适应性免疫反应。

DOI：
10.1128/jvi.00095-17
发表时间：
2017
期刊：
Journal of virology
影响因子：
5.4
作者：
Reeves,DanielB;Peterson,ChristopherW;Kiem,Hans-Peter;Schiffer,JoshuaT
通讯作者：
Schiffer,JoshuaT

Immune inactivation of anti-simian immunodeficiency virus chimeric antigen receptor T cells in rhesus macaques.

DOI：
10.1016/j.omtm.2021.06.008
发表时间：
2021-09-10
期刊：
Molecular therapy. Methods & clinical development
影响因子：
0
作者：
Haeseleer F;Fukazawa Y;Park H;Varco-Merth B;Rust BJ;Smedley JV;Eichholz K;Peterson CW;Mason R;Kiem HP;Roederer M;Picker LJ;Okoye AA;Corey L
通讯作者：
Corey L

Willingness to participate and take risks in HIV cure research: survey results from 400 people living with HIV in the US

参与艾滋病毒治疗研究并承担风险的意愿：对美国 400 名艾滋病毒感染者的调查结果

DOI：
10.1016/s2055-6640(20)30295-8
发表时间：
2017
期刊：
Journal of Virus Eradication
影响因子：
5.5
作者：
K. Dubé;D. Evans;L. Sylla;Jeff Taylor;B. Weiner;A. Skinner;H. Thirumurthy;J. Tucker;S. Rennie;S. Greene
通讯作者：
S. Greene

Engineering antibody-like inhibitors to prevent and treat HIV-1 infection.