Genetically Modified NKT Cells to Target Viral Reservoirs

Tulane University Of Louisiana, New Orleans LA

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Abstract

PROJECT SUMMARY HIV persistence despite long-term administration of potent viral-suppressive antiretroviral therapy (ART) remains a major impediment to HIV eradication and cure. Immunotherapeutic tools such as genetically modified T cells with chimeric antigen receptors (CAR) offer a new and potentially promising in vivo approach to specifically target and kill HIV-infected cells. The goal of this proposal is to genetically engineer anti-HIV CARs to invariant natural killer T (NKT) cells, with the aim of harnessing the immunotherapeutic potential of this unique innate T cell subset to target HIV-infected cells at tissue reservoir sites. Our specific aims are: SA#1. To evaluate in vitro expansion, signaling, and CTL activity of macaque NKT cells when transduced with CD4-CAR vectors containing Tc-specific intracellular signaling domains (NKT-CAR); and SA#2. To evaluate in vivo biodistribution, and persistence of adoptively transferred anti-HIV NKT-CARs and control Tc-CARs in macaques before and after SHIV infection.