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

Autor:	van Dinther D; 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. d.vandinther@vumc.nl., Lopez Venegas M; 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. m.lopezvenegas@vumc.nl.; DC4U B.V., De Corridor 21E, 3621 ZA Breukelen, The Netherlands. m.lopezvenegas@vumc.nl., Veninga H; 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. henrikeveninga@hotmail.com., Olesek K; 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. k.olesek@vumc.nl., Hoogterp L; 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. l.hoogterp@vumc.nl., Revet M; 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. mirjamrevet@hotmail.com., Ambrosini M; 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. m.ambrosini@vumc.nl.; DC4U B.V., De Corridor 21E, 3621 ZA Breukelen, The Netherlands. m.ambrosini@vumc.nl., Kalay H; 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. H.Kalay@vumc.nl., Stöckl J; Institute of Immunology, Center of Pathophysiology, Immunology and Infectiology, Medical University of Vienna, 1090 Vienna, Austria. johannes.stoeckl@meduniwien.ac.at., van Kooyk Y; 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. y.vankooyk@vumc.nl.; DC4U B.V., De Corridor 21E, 3621 ZA Breukelen, The Netherlands. y.vankooyk@vumc.nl., den Haan JMM; 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. j.denhaan@vumc.nl.
Jazyk:	angličtina
Zdroj:	Cancers [Cancers (Basel)] 2019 Feb 05; Vol. 11 (2). Date of Electronic Publication: 2019 Feb 05.
DOI:	10.3390/cancers11020183
Abstrakt:	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.
Databáze:	MEDLINE
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