Priming anti-tumor responses with MHC I single chain trimer vaccines (41.16)

Abstract

Abstract The inefficiency of the MHC I presentation pathway and the low affinity of some tumor peptide/MHC complexes can lead to a reduced density of tumor-associated peptide/MHC complexes on tumor cells, which can partly explain the failure to prime CTL (cytotoxic T lymphocyte) responses against tumors. Here, we are evaluating a set of MHC I Single Chain Trimers (SCTs) used in conjunction with dendritic cell (DC) or DNA vaccination for their ability to prime a CTL response specific for tumor antigens. A SCT consists of an MHC I molecule covalently linked to a peptide and our goal is to test whether tumor-associated antigen presentation by MHC I SCTs will result in better CTL priming and immune protection than more conventional peptide-specific vaccination protocols. The melanoma antigenic peptide TRP2 (Tyrosinase related protein 2, aa180-188) was chosen in this study for presentation on Kb SCTs; OVA-SCT (Kb-SIINFEKL) was chosen as a control. In vivo experiments suggest that mice vaccinated with TRP2 SCT-transduced DCs present better tumor protection, compared to controls. SCT vaccines, combined with Treg depletion are in progress to evaluate specific priming and tumor protection. Our preliminary data suggest that SCTs represent a promising technology capable of priming strong and specific CTL responses, with the potential of eliciting systemic tumor protection. Supported by the Arizona Biomedical Research Commission.