Exosomal cancer immunotherapy is independent of MHC molecules on exosomes
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Stefanie Hiltbrunner1,*, Pia Larssen1,*, Maria Eldh1, Maria-Jose Martinez-Bravo1, Arnika K. Wagner2, Mikael C.I. Karlsson2, Susanne Gabrielsson1
1Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, and Karolinska University Hospital, SE-171 76 Stockholm, Sweden
2Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden
*These authors have contributed equally to this work
Susanne Gabrielsson, email: [email protected]
Keywords: exosomes, immunotherapy, MHC class I, extracellular vesicles, cancer
Received: March 03, 2016 Accepted: April 28, 2016 Published: May 25, 2016
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.
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