Adjuvant autologous melanoma vaccine for macroscopic stage III disease: survival, biomarkers, and improved response to CTLA-4 blockade

dc.citation.epage8121985-12en_US
dc.citation.spage8121985-1en_US
dc.citation.volumeNumber2016en_US
dc.contributor.authorLotem, M.en_US
dc.contributor.authorMerims, S.en_US
dc.contributor.authorFrank, S.en_US
dc.contributor.authorHamburger, T.en_US
dc.contributor.authorNissan, A.en_US
dc.contributor.authorKadouri, L.en_US
dc.contributor.authorCohen, J.en_US
dc.contributor.authorStraussman, R.en_US
dc.contributor.authorEisenberg, G.en_US
dc.contributor.authorFrankenburg, S.en_US
dc.contributor.authorCarmon, E.en_US
dc.contributor.authorAlaiyan, B.en_US
dc.contributor.authorShneibaum, S.en_US
dc.contributor.authorAyyildiz, Z. O.en_US
dc.contributor.authorIsbilen, M.en_US
dc.contributor.authorSenses, K. M.en_US
dc.contributor.authorRon, I.en_US
dc.contributor.authorSteinberg, H.en_US
dc.contributor.authorSmith, Y.en_US
dc.contributor.authorShiloni, E.en_US
dc.contributor.authorGure, A. O.en_US
dc.contributor.authorPeretz, T.en_US
dc.date.accessioned2018-04-12T11:05:29Z
dc.date.available2018-04-12T11:05:29Z
dc.date.issued2016en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractBackground. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.en_US
dc.identifier.doi10.1155/2016/8121985en_US
dc.identifier.issn2314-8861
dc.identifier.urihttp://hdl.handle.net/11693/37186
dc.language.isoEnglishen_US
dc.publisherHindawi Limiteden_US
dc.relation.isversionofhttps://doi.org/10.1155/2016/8121985en_US
dc.source.titleJournal of Immunology Researchen_US
dc.subject2,4 dinitrophenolen_US
dc.subjectAutologous melanoma vaccineen_US
dc.subjectB Raf kinaseen_US
dc.subjectBCG vaccineen_US
dc.subjectCancer testis antigenen_US
dc.subjectCyclophosphamideen_US
dc.subjectCytotoxic T lymphocyte antigen 4en_US
dc.subjectIpilimumaben_US
dc.subjectMelanoma vaccineen_US
dc.subjectUnclassified drugen_US
dc.subjectAntineoplastic agenten_US
dc.subjectBiological markeren_US
dc.subjectCancer vaccineen_US
dc.subjectCytotoxic T lymphocyte antigen 4en_US
dc.subjectImmunological adjuvanten_US
dc.subjecttumor antigenen_US
dc.subjectCancer recurrenceen_US
dc.subjectCancer stagingen_US
dc.subjectCancer survivalen_US
dc.subjectComparative studyen_US
dc.subjectDelayed hypersensitivityen_US
dc.subjectDisease free survivalen_US
dc.subjectDrug safetyen_US
dc.subjectFemaleen_US
dc.subjectGene expressionen_US
dc.subjectHumanen_US
dc.subjectInjection site erythemaen_US
dc.subjectMajor clinical studyen_US
dc.subjectMaleen_US
dc.subjectMelanomaen_US
dc.subjectMelanoma metastasisen_US
dc.subjectOutcome assessmenten_US
dc.subjectOverall survivalen_US
dc.subjectPhase 2 clinical trialen_US
dc.subjectProspective studyen_US
dc.subjectTreatment durationen_US
dc.subjectVery elderlyen_US
dc.subjectAdolescenten_US
dc.subjectAnimalen_US
dc.subjectAntagonists and inhibitorsen_US
dc.subjectClinical trialen_US
dc.subjectCluster analysisen_US
dc.subjectKaplan Meier methoden_US
dc.subjectMetabolismen_US
dc.subjectMiddle ageden_US
dc.subjectMolecularly targeted therapyen_US
dc.subjectMortalityen_US
dc.subjectMouseen_US
dc.subjectMultimodality cancer therapyen_US
dc.subjectPathologyen_US
dc.subjectTreatment outcomeen_US
dc.subjectTumor cell lineen_US
dc.subjectVaccinationen_US
dc.subjectYoung adulten_US
dc.subjectAdjuvants, Immunologicen_US
dc.subjectAdolescenten_US
dc.subjectAged, 80 and overen_US
dc.subjectCombined Modality Therapyen_US
dc.subjectCTLA-4 Antigenen_US
dc.subjectGene Expression Profilingen_US
dc.titleAdjuvant autologous melanoma vaccine for macroscopic stage III disease: survival, biomarkers, and improved response to CTLA-4 blockadeen_US
dc.typeArticleen_US
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