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Activation of CD8+ T Cell Responses after Melanoma Antigen Targeting to CD169+ Antigen Presenting Cells in Mice and Humans

1
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
2
DC4U B.V., De Corridor 21E, 3621 ZA Breukelen, The Netherlands
3
Institute of Immunology, Center of Pathophysiology, Immunology and Infectiology, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
Cancers 2019, 11(2), 183; https://doi.org/10.3390/cancers11020183
Received: 30 November 2018 / Revised: 28 January 2019 / Accepted: 31 January 2019 / Published: 5 February 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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Abstract

The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs). In human and mouse spleen, we detected CD169+ cells at an equivalent location using immunofluorescence microscopy. Immunization with melanoma antigens conjugated to antibodies (Abs) specific for mouse CD169 efficiently induced gp100 and Trp2-specific T cell responses in mice. In HLA-A2.1 transgenic mice targeting of the human MART-1 peptide to CD169 induced strong MART-1-specific HLA-A2.1-restricted T cell responses. Human gp100 peptide conjugated to Abs specific for human CD169 bound to CD169-expressing monocyte-derived DCs (MoDCs) and resulted in activation of gp100-specific T cells. Together, these data indicate that Ab-mediated antigen targeting to CD169 is a potential strategy for the induction of melanoma-specific T cell responses in mice and in humans. View Full-Text
Keywords: macrophage; dendritic cell; cancer vaccines; melanoma; T cell responses; CD169; Siglec-1; sialoadhesin macrophage; dendritic cell; cancer vaccines; melanoma; T cell responses; CD169; Siglec-1; sialoadhesin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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van Dinther, D.; Lopez Venegas, M.; Veninga, H.; Olesek, K.; Hoogterp, L.; Revet, M.; Ambrosini, M.; Kalay, H.; Stöckl, J.; van Kooyk, Y.; den Haan, J.M.M. Activation of CD8+ T Cell Responses after Melanoma Antigen Targeting to CD169+ Antigen Presenting Cells in Mice and Humans. Cancers 2019, 11, 183.

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