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

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http://hdl.handle.net/10138/306973

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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

Titel: Oncolytic adenovirus drives specific immune response generated by a poly-epitope pDNA vaccine encoding melanoma neoantigens into the tumor site
Författare: Lopes, Alessandra; Feola, Sara; Ligot, Sophie; Fusciello, Manlio; Vandermeulen, Gaëlle; Préat, Véronique; Cerullo, Vincenzo
Upphovmannens organisation: Division of Pharmaceutical Biosciences
ImmunoViroTherapy Lab
Drug Research Program
University Management
Datum: 2019-07-10
Språk: eng
Sidantal: 14
Tillhör serie: Journal for Immunotherapy of Cancer
ISSN: 2051-1426
DOI: https://doi.org/10.1186/s40425-019-0644-7
Permanenta länken (URI): http://hdl.handle.net/10138/306973
Abstrakt: 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.
Subject: ACTIVATION
CANCER
Cancer
DNA vaccine
EFFICACY
IDENTIFICATION
INTERLEUKIN-2
Melanoma neoantigens
NATURAL-KILLER-CELLS
NK CELLS
Oncolytic adenovirus
RECEPTOR
RECRUITMENT
THERAPY
Tumor microenvironment
3122 Cancers
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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