Hiltbrunner, S;
Larssen, P;
Eldh, M;
Martinez-Bravo, M-J;
Wagner, AK;
Karlsson, MCI;
Gabrielsson, S;
(2016)
Exosomal cancer immunotherapy is independent of MHC molecules on exosomes.
Oncotarget
, 7
(25)
pp. 38707-38717.
10.18632/oncotarget.9585.
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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.
Type: | Article |
---|---|
Title: | Exosomal cancer immunotherapy is independent of MHC molecules on exosomes |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.18632/oncotarget.9585 |
Publisher version: | https://doi.org/10.18632/oncotarget.9585 |
Language: | English |
Additional information: | This work is licensed under a Creative Commons Attribution 3.0 License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, exosomes, immunotherapy, MHC class I, extracellular vesicles, cancer, CELL-DERIVED EXOSOMES, PEPTIDE-BASED VACCINE, CD8(+) CTL RESPONSES, DENDRITIC CELLS, ANTITUMOR IMMUNITY, IN-VIVO, ANTIGEN, COMPLEXES, MECHANISM |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
URI: | https://discovery.ucl.ac.uk/id/eprint/10041587 |
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