Novel Immune Assessment and Mouse Core

新型免疫评估和鼠标核心

基本信息

批准号：
8245039
负责人：
James L Riley
金额：
$ 26.7万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8245039
关键词：
Animal Model Biological Assay CCR5 gene CD4 Positive T Lymphocytes CD8B1 gene CXCR4 gene Cell Line Cells Clinical Clinical Trials Cloning Collaborations Communities Ensure Equipment Evolution Fee-for-Service Plans Fostering Future Gene-Modified Goals HIV HIV-1 HLA-A2 Antigen Human Immune Immune system Immunology Immunotherapy In Vitro Infection Investigation Lentivirus Vector Measures Modeling Mus Outcome Pediatric Hospitals Pennsylvania Performance Phase I Clinical Trials Philadelphia Play Poliomyelitis Principal Investigator Protocols documentation Rabies Reagent Recording of previous events Research Research Infrastructure Research Personnel Resistance Resources Role Rotavirus Safety Series Shapes Stem cells Structure T-Lymphocyte The Wistar Institute Treatment Efficacy Universities Vaccines Viral base bench to bedside design efficacy testing gene therapy in vivo in vivo Model mouse model novel prevent research study response safety testing

项目摘要

Core B, the Novel Immune Assessment and Mouse Core, provides immunological assay design and performance support, reagents, and humanized murine models to enable all 3 Projects in this IPCP to study gene therapy approaches to treating HIV-1 infection. The overall goal of this IPCP is to build an HIV resistant immune system. This Core directly supports this goal by establishing in vitro and in vivo models to test the safety and efficacy of gene-modified T cells. Dr. Riley is the Principal Investigator for the Core, and he will be responsible for ensuring that Core provides outstanding immunological and murine model support. Dr. Riley has had productive, long term collaborations with all of three of Project PIs and this will facilitate Core and Project interactions. For Project 1, Core B will conduct in vitro and in vivo functional assessment of native and enhanced TCRs. For Project 2, the Core will perform all of the immunoassessment for the clinical trials with an emphasis on measuring the function of infused SL9-specific TCR-transduced T cells. For Project 3, Core B will provide an in vivo model to measure viral evolution in response to agents that target CCR5 and/or CXCR4. Specific Aim 1: To generate immunological reagents supporting the investigations of Projects 1, 2 and 3. Specific Aim 2: To characterize HIV-1 specific TCR transduced T cells and ZFN modified T cells from Projects 1, 2 and 3. Specific Aim 3: To perform humanized mouse studies to determine the safety and therapeutic efficacy of cells generated by Projects 1, 2 and 3.

核心 B，即新型免疫评估和小鼠核心，提供免疫测定设计和性能支持、试剂和人源化小鼠模型，使本 IPCP 中的所有 3 个项目能够研究治疗 HIV-1 感染的基因治疗方法。该IPCP的总体目标是建立抗艾滋病毒的免疫系统。该核心通过建立体外和体内模型来测试基因修饰 T 细胞的安全性和有效性，从而直接支持这一目标。 Riley 博士是 Core 的首席研究员，他将负责确保 Core 提供出色的免疫学和小鼠模型支持。 Riley 博士与所有三名项目 PI 进行了富有成效的长期合作，这将促进核心和项目的互动。对于项目 1，核心 B 将对天然 TCR 和增强 TCR 进行体外和体内功能评估。对于项目 2，核心将执行临床试验的所有免疫评估，重点是测量输注的 SL9 特异性 TCR 转导 T 细胞的功能。对于项目 3，Core B 将提供一个体内模型来测量病毒对针对 CCR5 和/或 CXCR4 的药物的进化反应。具体目标 1：生成支持项目 1、2 和 3 的研究的免疫试剂。具体目标 2：表征项目 1、2 和 3 中的 HIV-1 特异性 TCR 转导 T 细胞和 ZFN 修饰 T 细胞。具体目标 3：进行人源化小鼠研究，以确定项目 1、2 和 3 产生的细胞的安全性和治疗功效。