VirTac, a modular lentiviral-based platform, elicits selective and marked expansion of HIV-, CMV- and SARS-CoV-2-specific T cell responses, validating its applications for adoptive T cell therapies 2374

Abstract Description New strategies to efficiently generate virus- and cancer-specific CD8 T cells are needed to increase antigenic breadth, efficacy and use of adoptive T-cell therapies for infectious diseases and cancer. We developed VirTac (VT), a modular lentivirus (LV)-based non-infectious immunotherapeutic platform to mimic features of APCs by presenting membrane proteins that elicit the selective expansion of antigen-specific CD8 T cells. We demonstrate that VT bearing single chain HLA-A*0201 MHC constructs presenting SL9 (HIV), NLV (CMV) or YLQ (CoV-2) peptides, either alone or combined with an agonist αCD28 scFv, can selectively modulate antigen-specific CD8 T cells. In vitro treatment of human donor PBMCs (n = 2-5) with SL9-, NLV- or YLQ-VT markedly expanded CD8 T cell populations specific for HIV (>20%), CMV (>87%) or CoV2 (>67%), respectively. Intravenous infusion of VT into NSG mice expanded HIV- and CMV-specific T cells by ∼30-fold; this response was enhanced in some of these donors by inclusion of the agonist αCD28 scFv in the VT. Antigen-specific T cells expanded with VT displayed potent antigen-specific cytotoxic activity, IFNγ and TNFα production and suppression of in vitro HIV or CMV infections. VT represents a highly modular platform that drives robust and selective ex vivo and in vivo expansion of antigen-specific CD8 T cells and enables diverse applications for enhancing adoptive cellular therapies to treat infectious diseases, autoimmune diseases and oncology indications. Funding Sources NIH R01 AI145024; NIH R01AI172607; NIH P30 AI124414 Topic Categories Vaccines and Immunotherapy (VAC)