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Exosomal cancer immunotherapy is independent of MHC molecules on exosomes

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. Green open access

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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
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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