Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site

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dc.contributor.author Lopes, Alessandra
dc.contributor.author Feola, Sara
dc.contributor.author Ligot, Sophie
dc.contributor.author Fusciello, Manlio
dc.contributor.author Vandermeulen, Gaëlle
dc.contributor.author Préat, Véronique
dc.contributor.author Cerullo, Vincenzo
dc.date.accessioned 2019-11-14T11:18:02Z
dc.date.available 2019-11-14T11:18:02Z
dc.date.issued 2019-07-10
dc.identifier.citation Lopes , A , Feola , S , Ligot , S , Fusciello , M , Vandermeulen , G , Préat , V & Cerullo , V 2019 , ' Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site ' , Journal for Immunotherapy of Cancer , vol. 7 , no. 1 , 174 . https://doi.org/10.1186/s40425-019-0644-7
dc.identifier.other PURE: 126267405
dc.identifier.other PURE UUID: 072f736b-47b8-4a24-b143-4c93b4ce7007
dc.identifier.other RIS: urn:4DD5B14767A71909B8932586F3B8EA94
dc.identifier.other RIS: Lopes2019
dc.identifier.other WOS: 000475646200002
dc.identifier.uri http://hdl.handle.net/10138/306973
dc.description.abstract Background: DNA vaccines against cancer held great promises due to the generation of a specific and long lasting immune response. However, when used as a single therapy, they are not able to drive the generated immune response into the tumor, because of the immunosuppressive microenvironment, thus limiting their use in humans. To enhance DNA vaccine efficacy, we combined a new poly-epitope DNA vaccine encoding melanoma tumor associated antigens and B16F1-specific neoantigens with an oncolytic virus administered intratumorally. Methods: Genomic analysis were performed to find specific mutations in B16F1 melanoma cells. The antigen gene sequences were designed according to these mutations prior to the insertion in the plasmid vector. Mice were injected with B16F1 tumor cells (n = 7-9) and therapeutically vaccinated 2, 9 and 16 days after the tumor injection. The virus was administered intratumorally at day 10, 12 and 14. Immune cell infiltration analysis and cytokine production were performed by flow cytometry, PCR and ELISPOT in the tumor site and in the spleen of animals, 17 days after the tumor injection. Results: The combination of DNA vaccine and oncolytic virus significantly increased the immune activity into the tumor. In particular, the local intratumoral viral therapy increased the NK infiltration, thus increasing the production of different cytokines, chemokines and enzymes involved in the adaptive immune system recruitment and cytotoxic activity. On the other side, the DNA vaccine generated antigen-specific T cells in the spleen, which migrated into the tumor when recalled by the local viral therapy. The complementarity between these strategies explains the dramatic tumor regression observed only in the combination group compared to all the other control groups. Conclusions: This study explores the immunological mechanism of the combination between an oncolytic adenovirus and a DNA vaccine against melanoma. It demonstrates that the use of a rational combination therapy involving DNA vaccination could overcome its poor immunogenicity. In this way, it will be possible to exploit the great potential of DNA vaccination, thus allowing a larger use in the clinic. en
dc.format.extent 14
dc.language.iso eng
dc.relation.ispartof Journal for Immunotherapy of Cancer
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ACTIVATION
dc.subject CANCER
dc.subject Cancer
dc.subject DNA vaccine
dc.subject EFFICACY
dc.subject IDENTIFICATION
dc.subject INTERLEUKIN-2
dc.subject Melanoma neoantigens
dc.subject NATURAL-KILLER-CELLS
dc.subject NK CELLS
dc.subject Oncolytic adenovirus
dc.subject RECEPTOR
dc.subject RECRUITMENT
dc.subject THERAPY
dc.subject Tumor microenvironment
dc.subject 3122 Cancers
dc.title Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site en
dc.type Article
dc.contributor.organization Division of Pharmaceutical Biosciences
dc.contributor.organization ImmunoViroTherapy Lab
dc.contributor.organization Drug Research Program
dc.contributor.organization University Management
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1186/s40425-019-0644-7
dc.relation.issn 2051-1426
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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