Original Research ARTICLE
TARGETING LONG SYNTHETIC PEPTIDES TO XCR1+ CROSS-PRESENTING DENDRITIC CELLS RESULTS IN SUPERIOR TUMOR CONTROL
- 1Faculty of Biology and Medicine, University of Lausanne, Switzerland
- 2Institute for Molecular Engineering, University of Chicago, United States
- 3Ben May Department for Cancer Research, Division of Biological Sciences, University of Chicago, United States
- 4Department of Fundamental Oncology, Faculty of Biology and Medicine, Université de Lausanne, Switzerland
Cross-presenting Xcr1+CD8 DCs are attractive APCs to target for therapeutic cancer vaccines, as they are able to take up and process antigen from dying tumor cells for their MHCI-restricted presentation to CD8 T cells. To this aim, we developed fusion proteins made of the Xcr1 ligand Xcl1 fused to an OVA synthetic long peptide (SLP) and IgG1 Fc fragment. We demonstrated the specific binding and uptake of the Xcl1 fusion proteins by Xcr1+ DCs. Most importantly, their potent adjuvant effect on the H-2Kb/OVA specific T cell response was associated with a sustained tumor control even against the poorly immunogenic B16-OVA melanoma tumor. The increased tumor protection correlated with higher tumor infiltration of antigen-specific CD8+ T cells, increased IFNγ production and degranulation potential. Altogether, these results demonstrate that therapeutic cancer vaccines may be greatly improved by the combination of SLP antigen and Xcl1 fusion proteins.
Keywords: Therapeutic cancer vaccine, Antigen Cross Presentation, XCR1+ dendritic cells, XCL1, Synthetic long peptide (SLP)
Received: 24 Aug 2018;
Accepted: 05 Feb 2019.
Edited by:Sandra Tuyaerts, KU Leuven, Belgium
Reviewed by:Even Fossum, Oslo University Hospital, Norway
Eric Tartour, Hôpital Européen Georges-Pompidou (HEGP), France
Jan Tavernier, Ghent University, Belgium
Copyright: © 2019 Botelho, Hubbell, Swartz, Donda and Romero. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Pedro Romero, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland, Pedro.Romero@hospvd.ch