I4C 2.0: Immunotherapy for Cure

I4C 2.0：免疫疗法治愈

基本信息

批准号：
10311894
负责人：
Dan H. Barouch
金额：
$ 490.47万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-16 至 2026-04-30
项目状态：
未结题

项目摘要

SUMMARY The goals of I4C 2.0 are to advance our scientific understanding of the viral reservoir and to develop immunologic strategies for HIV-1 remission and eradication by a highly collaborative and multifaceted research program involving partnerships among academia, industry, government, and the community. Our overall hypothesis is that multiple immunologic strategies will need to be explored and combined to achieve long-term, ART- free virologic control or complete virus eradication, with the goal of selecting combination regimens to advance into clinical development by the end of the proposed period of support. We propose three Research Foci, a Management and Operations Section, and a Community Engagement Section. Focus 1 (Mechanistic Basis of Reservoir Targeting and Viral Persistence) Aim 1. To define a virologic, immunologic, and transcriptomic signature of viral persistence and rebound and to determine how immunologic strategies target the viral reservoir in NHPs and humans Aim 2. To define drivers of clonal expansion and persistence of the replication-competent viral reservoir in NHPs and humans to enhance reservoir control and elimination Focus 2 (Novel Strategies for Sustained Virus Remission) Aim 1. To evaluate innovative immune engineering strategies that provide long-term T cell or Env-directed immune control, including therapeutic vaccines, CAR-T cells, and engineered B cells Aim 2. To combine approaches that augment humoral and cellular immune responses to achieve sustained immunosurveillance and long-term ART-free virologic control Focus 3 (Novel Strategies for Virus Eradication) Aim 1. To evaluate innovative strategies for rapid elimination of the majority of the viral reservoir, including improved LRAs combined with bNAbs, activated NK cells, and CAR-T cells Aim 2. To combine the most effective approach to rapidly eliminate the majority of the viral reservoir with sustained immunosurveillance to eliminate the residual viral reservoir Management and Operations (MO) Section Community Engagement (CE) Section

概括 I4C 2.0 的目标是增进我们对病毒库的科学理解并开发免疫学通过高度协作和多方面的研究计划制定缓解和根除 HIV-1 的策略涉及学术界、工业界、政府和社区之间的伙伴关系。我们的总体假设是需要探索和组合多种免疫策略以实现长期的、ART- 自由病毒学控制或完全根除病毒，目标是选择联合治疗方案在建议的支持期结束时进入临床开发。我们提出三个研究焦点、管理和运营部分以及社区参与部分。焦点1（储库靶向和病毒持久性的机制基础）目标 1. 定义病毒持续存在和反弹的病毒学、免疫学和转录组学特征，并确定免疫策略如何针对 NHP 和人类的病毒库目标 2. 确定 NHP 中具有复制能力的病毒库的克隆扩增和持久性的驱动因素和人类加强水库控制和消除焦点 2（持续病毒缓解的新策略）目标 1. 评估提供长期 T 细胞或 Env 导向的创新免疫工程策略免疫控制，包括治疗性疫苗、CAR-T 细胞和工程 B 细胞目标 2. 结合增强体液和细胞免疫反应的方法，以实现持续的免疫反应免疫监视和长期无ART病毒学控制焦点 3（消灭病毒的新策略）目标 1. 评估快速消除大部分病毒库的创新策略，包括改进的 LRA 与 bNAb、活化的 NK 细胞和 CAR-T 细胞相结合目标 2. 将快速消灭大部分病毒库的最有效方法与持续的免疫监视以消除残留的病毒库管理及营运 (MO) 科社区参与（CE）部分