Determining Efficacy of CAR T Cell Therapy to Cause Sustained Reduction of vRNA+ Cells in SIV Infected Rhesus macaques
Human immunodeficiency virus (HIV) continues to affect millions of lives despite being a subject of substantial research. HIV and simian immunodeficiency virus (SIV) replication concentrate within B cell follicles of secondary lymphoid tissues where virus-specific CD8 T cells tend to be excluded and, as a result, have limited the ability of virus-specific CD8 T cells to fully control viral replication. We hypothesized that chimeric antigen receptor (CAR) T cells specific for SIV and targeted for B cell follicles via expression of CXCR5 (B cell follicle homing molecule) may reduce the level of follicular virus replication in the SIV-infected rhesus macaques animal model of HIV. To test this hypothesis, we utilized RNAscope in situ hybridization combined with immunohistochemistry followed by confocal imaging and quantitative image analysis to analyze lymph node tissue biopsied from animals at 2, 6, 14, 28, and 60 days post-treatment and compared that to a control untreated group. We quantified CAR/CXCR5-T cells and SIV-infected cells in the follicular and extrafollicular regions of lymph nodes. We found CAR/CXCR5 CAR-T cells are most abundant at 2 and 6 days post-treatment and persisted up to 28 days post-treatment. Two of three treated animals displayed sustained control of SIV infection. These animals had fewer vRNA+ cells in follicular and extrafollicular areas at 28 days post-treatment as compared to the untreated animals and the one animal that did not sustain control. These findings support our hypothesis that CAR/CXCR5-T cells may lead to a sustained reduction of vRNA+ cells.