Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma
<b>Background/Objectives</b>: The revolution for the treatment of melanoma came with the approval of checkpoint blockade antibodies. However, a substantial proportion of patients show primary or secondary resistance to this type of immunotherapy, indicating the need for alternative thera...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/2076-393X/13/4/346 |
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| author | Athanasios Seretis Lukas Amon Christoph H. Tripp Giuseppe Cappellano Florian Hornsteiner Sophie Dieckmann Janine Vierthaler Daniela Ortner-Tobider Markus Kanduth Rita Steindl Louis Boon Joke M. M. den Haan Christian H. K. Lehmann Diana Dudziak Patrizia Stoitzner |
| author_facet | Athanasios Seretis Lukas Amon Christoph H. Tripp Giuseppe Cappellano Florian Hornsteiner Sophie Dieckmann Janine Vierthaler Daniela Ortner-Tobider Markus Kanduth Rita Steindl Louis Boon Joke M. M. den Haan Christian H. K. Lehmann Diana Dudziak Patrizia Stoitzner |
| author_sort | Athanasios Seretis |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: The revolution for the treatment of melanoma came with the approval of checkpoint blockade antibodies. However, a substantial proportion of patients show primary or secondary resistance to this type of immunotherapy, indicating the need for alternative therapeutic strategies. Dendritic cells (DCs) of the skin are prime targets for vaccination approaches due to their potential to prime naïve T cells and their accessibility. This study aimed to develop and evaluate novel vaccines targeting the C-type lectin receptor DEC-205 to deliver melanoma-associated antigenic peptides to skin DCs. <b>Methods</b>: We cloned MHC-I-restricted peptides from the glycoprotein (gp)100<sub>25–33</sub> and Tyrosinase-related protein (trp)2<sub>180–188</sub> into the DEC-205 antibody sequence with modified peptide cutting sites from the OVA<sub>257–264</sub> SIINFEKL peptide. We tested their potential to induce CD8<sup>+</sup> T cell responses in both in vitro and in vivo settings. Tumor growth inhibition was evaluated in the transplantable B16.OVA melanoma murine model using a multi-epitope DC-based vaccine combining both peptides. <b>Results</b>: The cross-presentation of both gp100 and trp2 peptides was confirmed in vivo when peptide sequences were flanked by the OVA<sub>257–264</sub> peptide cutting sites. Moreover, the combination of both antigenic peptides into a multi-epitope DC vaccine was required to inhibit B16.OVA melanoma growth. <b>Conclusions</b>: Our findings suggest that a DC-targeted vaccination approach using multiple epitopes deriving from melanoma antigens could represent a promising strategy for melanoma therapy. |
| format | Article |
| id | doaj-art-60c6792214e44b1fb1a6e55fef21c995 |
| institution | DOAJ |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-60c6792214e44b1fb1a6e55fef21c9952025-08-20T03:13:57ZengMDPI AGVaccines2076-393X2025-03-0113434610.3390/vaccines13040346Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of MelanomaAthanasios Seretis0Lukas Amon1Christoph H. Tripp2Giuseppe Cappellano3Florian Hornsteiner4Sophie Dieckmann5Janine Vierthaler6Daniela Ortner-Tobider7Markus Kanduth8Rita Steindl9Louis Boon10Joke M. M. den Haan11Christian H. K. Lehmann12Diana Dudziak13Patrizia Stoitzner14Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91052 Erlangen, GermanyDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, AustriaJJP Biologics, 00-728 Warsaw, PolandDepartment of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NeatherlandsLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91052 Erlangen, GermanyLaboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91052 Erlangen, GermanyDepartment of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, Austria<b>Background/Objectives</b>: The revolution for the treatment of melanoma came with the approval of checkpoint blockade antibodies. However, a substantial proportion of patients show primary or secondary resistance to this type of immunotherapy, indicating the need for alternative therapeutic strategies. Dendritic cells (DCs) of the skin are prime targets for vaccination approaches due to their potential to prime naïve T cells and their accessibility. This study aimed to develop and evaluate novel vaccines targeting the C-type lectin receptor DEC-205 to deliver melanoma-associated antigenic peptides to skin DCs. <b>Methods</b>: We cloned MHC-I-restricted peptides from the glycoprotein (gp)100<sub>25–33</sub> and Tyrosinase-related protein (trp)2<sub>180–188</sub> into the DEC-205 antibody sequence with modified peptide cutting sites from the OVA<sub>257–264</sub> SIINFEKL peptide. We tested their potential to induce CD8<sup>+</sup> T cell responses in both in vitro and in vivo settings. Tumor growth inhibition was evaluated in the transplantable B16.OVA melanoma murine model using a multi-epitope DC-based vaccine combining both peptides. <b>Results</b>: The cross-presentation of both gp100 and trp2 peptides was confirmed in vivo when peptide sequences were flanked by the OVA<sub>257–264</sub> peptide cutting sites. Moreover, the combination of both antigenic peptides into a multi-epitope DC vaccine was required to inhibit B16.OVA melanoma growth. <b>Conclusions</b>: Our findings suggest that a DC-targeted vaccination approach using multiple epitopes deriving from melanoma antigens could represent a promising strategy for melanoma therapy.https://www.mdpi.com/2076-393X/13/4/346dendritic cellsC-type lectin receptorsimmunotherapymelanoma antigensDC-targeted therapy |
| spellingShingle | Athanasios Seretis Lukas Amon Christoph H. Tripp Giuseppe Cappellano Florian Hornsteiner Sophie Dieckmann Janine Vierthaler Daniela Ortner-Tobider Markus Kanduth Rita Steindl Louis Boon Joke M. M. den Haan Christian H. K. Lehmann Diana Dudziak Patrizia Stoitzner Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma Vaccines dendritic cells C-type lectin receptors immunotherapy melanoma antigens DC-targeted therapy |
| title | Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma |
| title_full | Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma |
| title_fullStr | Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma |
| title_full_unstemmed | Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma |
| title_short | Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma |
| title_sort | multi epitope dc vaccines with melanoma antigens for immunotherapy of melanoma |
| topic | dendritic cells C-type lectin receptors immunotherapy melanoma antigens DC-targeted therapy |
| url | https://www.mdpi.com/2076-393X/13/4/346 |
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