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.
Core B has developed the reagents and expertise to study HIV-1 infection in primary human cells in vitro and in vivo. This core will compare several approaches to gene-modify cells for their ability to control HIV-1 and restore the immune system. These studies will shape future Phase I clinical trials.
|Didigu, Chuka A; Wilen, Craig B; Wang, Jianbin et al. (2014) Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. Blood 123:61-9|
|Richardson, Max W; Guo, Lili; Xin, Frances et al. (2014) Stabilized human TRIM5? protects human T cells from HIV-1 infection. Mol Ther 22:1084-95|
|Maier, Dawn A; Brennan, Andrea L; Jiang, Shuguang et al. (2013) Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Hum Gene Ther 24:245-58|
|Didigu, Chukwuka A; Doms, Robert W (2012) Novel approaches to inhibit HIV entry. Viruses 4:309-24|
|Scholler, John; Brady, Troy L; Binder-Scholl, Gwendolyn et al. (2012) Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med 4:132ra53|
|Wilen, Craig B; Wang, Jianbin; Tilton, John C et al. (2011) Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases. PLoS Pathog 7:e1002020|
|Cannon, Paula; June, Carl (2011) Chemokine receptor 5 knockout strategies. Curr Opin HIV AIDS 6:74-9|
|Francica, Joseph R; Varela-Rohena, Angel; Medvec, Andrew et al. (2010) Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS Pathog 6:e1001098|
|Mukherjee, Rithun; Plesa, Gabriela; Sherrill-Mix, Scott et al. (2010) HIV sequence variation associated with env antisense adoptive T-cell therapy in the hNSG mouse model. Mol Ther 18:803-11|
|June, Carl H; Blazar, Bruce R; Riley, James L (2009) Engineering lymphocyte subsets: tools, trials and tribulations. Nat Rev Immunol 9:704-16|
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