Exosomal cancer immunotherapy is independent of MHC molecules on exosomes

// Stefanie Hiltbrunner 1, * , Pia Larssen 1, * , Maria Eldh 1 , Maria-Jose Martinez-Bravo 1 , Arnika K. Wagner 2 , Mikael C.I. Karlsson 2 , Susanne Gabrielsson 1 1 Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden * These authors have contributed equally to this work Correspondence to: Susanne Gabrielsson, email: susanne.gabrielsson@ki.se Keywords: exosomes, immunotherapy, MHC class I, extracellular vesicles, cancer Received: March 03, 2016     Accepted: April 28, 2016     Published: May 25, 2016 ABSTRACT Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI -/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans.