I4C 2.0: Immunotherapy for Cure

I4C 2.0：免疫疗法治愈

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10311894
• 关键词: Academia; Active Immunization; Agonist; B-Lymphocytes; Clonal Expansion; Communities; Community Networks; Disease remission; Engineering; Ensure; Feedback; Financial Support; Goals; Government; HIV-1; Human; Immune; Immune response; Immunologic Surveillance; Immunologics; Immunotherapy; Industry; Logistics; Macaca mulatta; Monkeys; Natural Killer Cells; Passive Immunization; Regimen; Research; Residual state; Resources; SIV; Sampling; T-Lymphocyte; TLR7 gene; TimeLine; United States National Institutes of Health; Vaccine Therapy; Viral; Viral reservoir; Virus; base; chimeric antigen receptor T cells; clinical development; community engagement; immunoengineering; improved; innovation; neutralizing antibody; novel strategies; operation; prevent; programs; simian human immunodeficiency virus; therapeutic vaccine; transcriptomics; viral rebound; virology

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的目标是提高我们对病毒储层的科学理解并发展免疫学 高度协作和多方面的研究计划，HIV-1缓解和消除HIV-1的策略 涉及学术界，工业，政府和社区之间的伙伴关系。我们的总体假设是 需要探索和合并多种免疫策略，以实现长期的艺术 自由病毒控制或完全消除病毒，目的是选择组合方案 在拟议的支持期结束之前，进入临床发展。我们提出了三个 研究焦点，管理和运营部分以及社区参与部分。 焦点1（水库靶向和病毒持久性的机械基础） 目的1。定义病毒持久性和反弹的病毒，免疫和转录组签名 确定免疫学策略如何针对NHP和人类的病毒储存 目的2。定义NHP中克隆膨胀的驱动因素和复制能力的病毒储层的持久性 和人类增强储层控制和消除 焦点2（持续病毒缓解的新型策略） 目的1。评估提供长期T细胞或ENV指导的创新免疫工程策略 免疫控制，包括治疗疫苗，CAR-T细胞和工程B细胞 目的2。结合方法来增强体液和细胞免疫反应以实现持续的方法 免疫监护和长期无艺术病毒学控制 焦点3（消除病毒的新策略） 目的1。评估创新策略，以快速消除大多数病毒储层，包括 改进的LRA结合了BNAB，活化的NK细胞和CAR-T细胞 目标2。结合最有效的方法，以快速消除大多数病毒储层 持续的免疫监视以消除残留的病毒储量 管理与运营（MO）部分 社区参与（CE）部分