Tu117 - Development of Nanoscale Artificial Antigen-presenting Cells as Novel Treatment for Type 1 Diabetes

Jack Ragheb – NexImmune Inc.; Aniket Wadajkar – NexImmune Inc.; Sojung Kim – NexImmune Inc.; Mathias Oelke – NexImmune Inc.; Kevan Herold – Immunobiology – Yale University School of Medicine

Abstract Text: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease and its pathogenesis involves autoantigen-specific CD8+ T cells destroying insulin-producing beta cells in the pancreas. Here, we used a novel nanoscale Artificial Immune Modulation (AIM) platform developed by NexImmune. With this platform, T1D antigenic peptides presented on Class I MHC molecules alone or in combination with 2nd signal ligands are affixed to 60-80 nm nanoparticles (nps) composed of the polymer, polylactic acid - polyethylene glycol (PLA-PEG). The AIM nps mimic antigen-presenting cells and direct a specific T cell-mediated immune response. Our data show that murine pmel-1 CD8+ T cells co-cultured with Db/gp100-PDL1-Ig nps secreted significantly lower levels of IL-2 and IFN-gamma in vitro compared to those treated with either uncoated nps or non-specific control nps (Db/unload-PDL1-Ig). Moreover, human MART-1 CD8+ T cells incubated with HLA/MART-1-PDL1-Ig nps had significantly diminished in vitro killing activity of peptide loaded target cells, compared to the CD8+ T cells treated with nps coated with either peptide alone or 2nd signal (PDL1-Ig) only. These results suggest that PDL1-Ig AIM nps inhibit function of CD8+ T cells in vitro in an antigen-specific manner. We then set out to investigate the effect of PDL1-Ig AIM nps using transgenic RIP-mOVA mouse model. RIP-mOVA recipients of OT-I CD8+ T cells treated by Kb/OVA-PDL1-Ig nps have been protected from autoimmune diabetes compared to the mice treated by uncoated nps (P=0.049). This result suggests inhibition of adoptively transferred pathogenic CD8+ T cells by PDL1-Ig AIM nps in vivo.