Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy

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dc.citation.issue4
dc.citation.volume65
dc.contributor.authorMedrano, Ruan Felipe Vieira
dc.contributor.authorCatani, Joao Paulo Portela
dc.contributor.authorRibeiro, Aline Hunger
dc.contributor.authorTomaz, Samanta Lopes [UNIFESP]
dc.contributor.authorMerkel, Christian A.
dc.contributor.authorCostanzi-Strauss, Eugenia
dc.contributor.authorStrauss, Bryan E.
dc.coverageNew York
dc.date.accessioned2020-07-22T13:23:15Z
dc.date.available2020-07-22T13:23:15Z
dc.date.issued2016
dc.description.abstractPreviously, we combined p19(Arf) (Cdkn2a, tumor suppressor protein) and interferon beta (IFN-beta, immunomodulatory cytokine) gene transfer in order to enhance cell death in a murine model of melanoma. Here, we present evidence of the immune response induced when B16 cells succumbing to death due to treatment with p19(Arf) and IFN-beta are applied in vaccine models. Use of dying cells for prophylactic vaccination was investigated, identifying conditions for tumor-free survival. After combined p19(Arf) and IFN-beta treatment, we observed immune rejection at the vaccine site in immune competent and nude mice with normal NK activity, but not in NOD-SCID and dexamethasone immunosuppressed mice (NK deficient). Combined treatment induced IL-15, ULBP1, FAS/APO1 and KILLER/DR5 expression, providing a mechanism for NK activation. Prophylactic vaccination protected against tumor challenge, where markedly delayed progression and leukocyte infiltration were observed. Analysis of primed lymphocytes revealed secretion of TH1-related cytokines and depletion protocols showed that both CD4(+) and CD8(+) T lymphocytes are necessary for immune protection. However, application of this prophylactic vaccine where cells were treated either with IFN-beta alone or combined with p19(Arf) conferred similar immune protection and cytokine activation, yet only the combination was associated with increased overall survival. In a therapeutic vaccine protocol, only the combination was associated with reduced tumor progression. Our results indicate that by harnessing cell death in an immunogenic context, our p19(Arf) and IFN-beta combination offers a clear advantage when both genes are included in the vaccine and warrants further development as a novel immunotherapy for melanoma.en
dc.description.affiliationUniv Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Viral Vector Lab,Ctr Invest Translac Oncol LIM24, Av Dr Arnaldo 251,8th Floor, BR-01246000 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Anim Care Facil, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Gene Therapy Lab, Inst Ciencias Biomed 1, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation
dc.description.sponsorshipIDFAPESP: 13/25167-5
dc.description.sponsorshipIDFAPESP: 11/50911-4
dc.description.sponsorshipIDFAPESP: 13/09474-5
dc.description.sponsorshipIDFAPESP: 11/10656-5
dc.description.sponsorshipIDFAPESP: 14/11524-3
dc.format.extent371-382
dc.identifierhttp://dx.doi.org/10.1007/s00262-016-1807-8
dc.identifier.citationCancer Immunology Immunotherapy. New York, v. 65, n. 4, p. 371-382, 2016.
dc.identifier.doi10.1007/s00262-016-1807-8
dc.identifier.issn0340-7004
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56126
dc.identifier.wosWOS:000373952700002
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofCancer Immunology Immunotherapy
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectCell deathen
dc.subjectp19Arfen
dc.subjectInterferon betaen
dc.subjectImmunotherapyen
dc.subjectMelanomaen
dc.subjectAdenovirusen
dc.titleVaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapyen
dc.typeinfo:eu-repo/semantics/article
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