2011
Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation
Magaldi TG, Almstead LL, Bellone S, Prevatt EG, Santin AD, DiMaio D. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation. Virology 2011, 422: 114-124. PMID: 22056390, PMCID: PMC3229657, DOI: 10.1016/j.virol.2011.10.012.Peer-Reviewed Original ResearchConceptsCervical carcinoma cellsCervical cancer cellsHuman papillomavirus E6Human cervical carcinoma cellsCarcinoma cellsPrimary cervical cancer cellsCancer cellsPapillomavirus E6Cervical carcinoma cell linesE2 proteinHuman cervical cancer cellsCarcinoma cell linesE7 expressionE7 oncogenesLow passage numberSerum-free conditionsCell surface receptorsSV40 infectionTumor suppressor pathwayCell linesPrimary cellsViral vectorsE6Suppressor pathwayPassage number
2009
Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines
Bellone S, El-Sahwi K, Cocco E, Casagrande F, Cargnelutti M, Palmieri M, Bignotti E, Romani C, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines. Journal Of Virology 2009, 83: 6779-6789. PMID: 19386711, PMCID: PMC2698533, DOI: 10.1128/jvi.02443-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCancer VaccinesCapsid ProteinsCell Line, TumorDendritic CellsFemaleGene Expression ProfilingHuman papillomavirus 16HumansMiddle AgedOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsRepressor ProteinsRNA, ViralT-Lymphocytes, CytotoxicUterine Cervical NeoplasmsYoung AdultConceptsCervical cancer patientsCytotoxic T lymphocytesAutologous tumor cellsCancer patientsDendritic cellsT lymphocytesL1 VLPsCervical cancerTumor cellsE7 RNADendritic cell-based therapeutic vaccineE7-specific cytotoxic T lymphocytesHPV-16 positive cervical cancerCell-mediated immune responsesExpression levelsAutologous dendritic cellsHPV-16 VLPPromising prophylactic vaccineE7-specific CD8Human papillomavirus infectionT lymphocyte responsesStrong cytolytic activityTreatment of patientsPeripheral blood lymphocytesPrimary cervical tumors
2008
A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells
Wang X, Santin AD, Bellone S, Gupta S, Nakagawa M. A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells. Cancer Immunology, Immunotherapy 2008, 58: 301-308. PMID: 18446336, PMCID: PMC2782377, DOI: 10.1007/s00262-008-0525-2.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen PresentationCancer VaccinesCD4 AntigensDendritic CellsDose-Response Relationship, DrugEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHuman papillomavirus 16Human papillomavirus 18HumansMolecular Sequence DataNeoplasm StagingOncogene Proteins, ViralPapillomavirus E7 ProteinsSignal TransductionT-LymphocytesUterine Cervical NeoplasmsConceptsT cell epitopesCD4 T cell epitopesT cell responsesT cell clonesHPV 16T cell linesDose escalation phase I clinical trialPeripheral blood mononuclear cellsE7 proteinPositive T-cell responsesPhase I clinical trialAutologous mature DCDendritic cell vaccinationIIA cervical cancerCervical cancer patientsIFN-γ secretionBlood mononuclear cellsHuman papillomavirus type 16Papillomavirus type 16Cell vaccinationStage IBDendritic cellsMature DCsCervical cancerELISPOT assay
2007
Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial
Santin AD, Bellone S, Palmieri M, Zanolini A, Ravaggi A, Siegel ER, Roman JJ, Pecorelli S, Cannon MJ. Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial. Journal Of Virology 2007, 82: 1968-1979. PMID: 18057249, PMCID: PMC2258728, DOI: 10.1128/jvi.02343-07.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, ViralAntibody FormationCancer VaccinesCarcinomaCD4-Positive T-LymphocytesDendritic CellsDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleHemocyaninsHumansImmunity, CellularNeoplasm StagingOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus VaccinesRecombinant ProteinsUterine Cervical NeoplasmsVaccinationConceptsCervical cancer patientsIIA cervical cancer patientsDendritic cell vaccinationHuman papillomavirus type 16Cancer patientsDC vaccinationStage IBPapillomavirus type 16Cell vaccinationE7 antigenType 16Delayed-type hypersensitivity reactionEnzyme-linked immunosorbent spotHPV E7 antigenLimited tumor burdenT-cell countsEvidence of diseaseIIA cervical cancerT cell responsesKeyhole limpet hemocyaninEnzyme-linked immunosorbentHPV16/18 E7Vaccine doseAutologous DCsDTH responseAdvances in dendritic cell-based therapeutic vaccines for cervical cancer
Bellone S, Pecorelli S, Cannon MJ, Santin AD. Advances in dendritic cell-based therapeutic vaccines for cervical cancer. Expert Review Of Anticancer Therapy 2007, 7: 1473-1486. PMID: 17944571, DOI: 10.1586/14737140.7.10.1473.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlphapapillomavirusAnimalsAntigen PresentationAntigens, ViralCancer VaccinesClinical Trials as TopicCombined Modality TherapyDendritic CellsDisease ProgressionDNA-Binding ProteinsFemaleHumansMaleMiceNeoplasmsOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsPeptide FragmentsRepressor ProteinsT-Lymphocyte SubsetsUterine Cervical NeoplasmsConceptsCervical cancerDendritic cellsMetastatic diseaseTherapeutic vaccinesDendritic cell-based therapeutic vaccineE7 oncoproteinsPowerful antigen-presenting cellsRecurrent/metastatic diseasePrimary T cell responsesAutologous dendritic cellsInvasive cervical cancerHuman papillomavirus infectionT cell responsesTherapeutic clinical trialsTumor-specific target antigensAntigen-presenting cellsImportant risk factorImportant health problemNovel therapeutic strategiesPapillomavirus infectionRadical surgeryCervical dysplasiaCancer deathRisk factorsClinical trials
2006
Recognition of a cervical cancer derived tumor cell line by a human papillomavirus type 16 E6 52-61-specific CD8 T cell clone.
Kim KH, Dishongh R, Santin AD, Cannon MJ, Bellone S, Nakagawa M. Recognition of a cervical cancer derived tumor cell line by a human papillomavirus type 16 E6 52-61-specific CD8 T cell clone. Cancer Immunology Research 2006, 6: 9. PMID: 16808432.Peer-Reviewed Original ResearchConceptsT cell clonesEnzyme-linked immunospotCervical cancerTumor cell linesCell clonesHomologous epitopesCell linesHigh-risk human papillomavirus (HPV) typesIFN-gamma enzyme-linked immunospotCD8 T cell clonesHigh-risk HPV typesCervical cancer patientsIFN-gamma secretionHuman papillomavirus typesChromium release assaysHLA class IHigh risk HPV sequencesPrimary tumor cell linesAddition of antigenLevel of killingHLA-B57HPV 35Specific CD8HPV typesELISPOT assayCorrelation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients
Ravaggi A, Romani C, Pasinetti B, Tassi RA, Bignotti E, Bandiera E, Odicino FE, Ragnoli M, Donzelli C, Falchetti M, Calza S, Santin AD, Pecorelli S. Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients. Archives Of Virology 2006, 151: 1899-1916. PMID: 16732494, DOI: 10.1007/s00705-006-0787-y.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralAntibody SpecificityBiomarkersBiotinCancer VaccinesCarcinomaDisease ProgressionDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin GOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus VaccinesPrecancerous ConditionsRecombinant ProteinsSensitivity and SpecificityStreptavidinUterine Cervical NeoplasmsVaccinationConceptsCervical cancer patientsCancer patientsHealthy womenHuman papillomavirusE7 oncoproteinsPre-invasive neoplasiaAutologous dendritic cellsSerological immune responsesCervical cancer developmentCapture ELISA methodType of responseHPV 16/18Clinical characteristicsDendritic cellsAntibody levelsAntibody inductionCervical carcinomaSerological evaluationAntibody prevalenceImmune responseAdjunctive toolPatientsCancer developmentELISA methodPotential marker
2005
HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities
Santin AD, Bellone S, Palmieri M, Ravaggi A, Romani C, Tassi R, Roman JJ, Burnett A, Pecorelli S, Cannon MJ. HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecologic Oncology 2005, 100: 469-478. PMID: 16249018, DOI: 10.1016/j.ygyno.2005.09.040.Peer-Reviewed Original ResearchConceptsCervical cancer patientsStandard treatment modalityAutologous dendritic cellsT cell responsesDendritic cellsCancer patientsTreatment modalitiesHPV16/18 E7Clinical responseIFN-gammaAutologous monocyte-derived dendritic cellsE7 oncoproteinsLate-stage cervical cancer patientsCell responsesMonocyte-derived dendritic cellsHuman recombinant interleukin-2Active vaccination strategiesHPV18 E7 oncoproteinLimited tumor burdenTreatment-induced immunosuppressionAutologous tumor cellsDendritic cell vaccinationObjective clinical responsesEarly-stage diseaseType hypersensitivity reaction
2003
Induction of tumor-specific cytotoxicity in tumor infiltrating lymphocytes by HPV16 and HPV18 E7-pulsed autologous dendritic cells in patients with cancer of the uterine cervix
Santin AD, Bellone S, Palmieri M, Bossini B, Roman JJ, Cannon MJ, Bignotti E, Canè S, Pecorelli S. Induction of tumor-specific cytotoxicity in tumor infiltrating lymphocytes by HPV16 and HPV18 E7-pulsed autologous dendritic cells in patients with cancer of the uterine cervix. Gynecologic Oncology 2003, 89: 271-280. PMID: 12713991, DOI: 10.1016/s0090-8258(03)00083-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultCytotoxicity, ImmunologicDendritic CellsDNA-Binding ProteinsFemaleFlow CytometryHumansImmunotherapy, AdoptiveInterferon-gammaInterleukin-4LeukocytesLymphocytes, Tumor-InfiltratingMembrane ProteinsOncogene Proteins, ViralPapillomavirus E7 ProteinsReceptors, Antigen, T-CellT-Lymphocytes, CytotoxicUterine Cervical NeoplasmsConceptsAutologous dendritic cellsAutologous tumor cellsCervical cancer patientsDendritic cellsPeripheral bloodT cellsTumor-specific cytotoxicityCancer patientsAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesAutologous tumor target cellsType 1 cytokine biasAnti-HLA class ICytotoxic T lymphocyte responsesIFN-gamma-positive cellsTwo-color flow cytometric analysisVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesTumor cellsAdoptive T-cell immunotherapyHPV18 E7 oncoproteinTumor-specific CTLsIntracellular cytokine expressionStandard treatment modalityT lymphocyte responsesT cell populations
2002
Vaccination with HPV-18 E7–Pulsed Dendritic Cells in a Patient with Metastatic Cervical Cancer
Santin AD, Bellone S, Gokden M, Cannon MJ, Parham GP. Vaccination with HPV-18 E7–Pulsed Dendritic Cells in a Patient with Metastatic Cervical Cancer. New England Journal Of Medicine 2002, 346: 1752-1753. PMID: 12037163, DOI: 10.1056/nejm200205303462219.Peer-Reviewed Original Research
2001
Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells.
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman JJ, Jayaprabhu S, Pecorelli S, Parham GP, Cannon MJ. Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells. Clinical Cancer Research 2001, 7: 804s-810s. PMID: 11300476.Peer-Reviewed Original ResearchMeSH KeywordsCD56 AntigenCD8-Positive T-LymphocytesCell LineDendritic CellsDNA-Binding ProteinsFemaleFlow CytometryHLA-A2 AntigenHumansImmunotherapyInterferon-gammaMembrane GlycoproteinsOncogene Proteins, ViralPapillomavirus E7 ProteinsPerforinPhenotypePore Forming Cytotoxic ProteinsTime FactorsT-Lymphocytes, CytotoxicTumor Cells, CulturedUterine Cervical NeoplasmsConceptsAntigen-specific CTL responsesE7-specific CD8Dendritic cellsTumor target cellsHPV 16CTL responsesHLA-A2Lymphoblastoid cell linesCD56 expressionTumor cellsHealthy individualsType 1 cytokine profileAnti-HLA class IHLA-A2 monoclonal antibodyAutologous dendritic cellsE7-specific CTLExpression of CD56Subset of CD8Human papillomavirus infectionTarget cellsImportant risk factorHigh cytolytic activityCervical cancer cell linesIntracellular perforin expressionCell lines
2000
Binding of the human papillomavirus type 16 E7 oncoprotein and the adeno-associated virus Rep78 major regulatory protein in vitro and in yeast and the potential for downstream effects.
Hermonat PL, Santin AD, Zhan D. Binding of the human papillomavirus type 16 E7 oncoprotein and the adeno-associated virus Rep78 major regulatory protein in vitro and in yeast and the potential for downstream effects. Human Virology 2000, 3: 113-24. PMID: 10881991.Peer-Reviewed Original ResearchMeSH KeywordsAlanineBinding SitesBlotting, WesternChromatography, AffinityDependovirusDNA PrimersDNA, ComplementaryDNA, ViralDNA-Binding ProteinsHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsProtein BindingRecombinant Fusion ProteinsTATA-Binding Protein Associated FactorsTATA-Box Binding ProteinTranscription Factor TFIIDTranscription FactorsViral ProteinsYeastsConceptsAAV life cycleHuman papillomavirusTerminal repeat DNACompetitive affinity chromatographyCancer-promoting activityRep78E7 oncoproteinsAAVRep78 proteinDownstream effectsHPV-16 E7 oncoproteinSeries of aminoHuman papillomavirus type 16 E7 oncoproteinHPV 16/18Cervical cancerHPV 16Variety of proteinsType 1Bovine papillomavirus type 1P97 promoterOncogenic transformationPapillomavirus type 1AdenoPotential downstream effectsDosage-dependent manner
1999
Binding of the Human Papillomavirus Type 16 p97 Promoter by the Adeno-associated Virus Rep78 Major Regulatory Protein Correlates with Inhibition*
Zhan D, Santin A, Liu Y, Parham G, Li C, Meyers C, Hermonat P. Binding of the Human Papillomavirus Type 16 p97 Promoter by the Adeno-associated Virus Rep78 Major Regulatory Protein Correlates with Inhibition*. Journal Of Biological Chemistry 1999, 274: 31619-31624. PMID: 10531369, DOI: 10.1074/jbc.274.44.31619.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBovine papillomavirus 1Cell Transformation, NeoplasticCell Transformation, ViralChromatography, AffinityColony-Forming Units AssayDependovirusDNA-Binding ProteinsGene Expression Regulation, ViralMolecular Sequence DataMutationOncogene Proteins, ViralPapillomaviridaePromoter Regions, GeneticProtein BindingRepetitive Sequences, Nucleic AcidRepressor ProteinsViral ProteinsInduction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer
Santin A, Hermonat P, Ravaggi A, Chiriva-Internati M, Zhan D, Pecorelli S, Parham G, Cannon M. Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer. Journal Of Virology 1999, 73: 5402-5410. PMID: 10364287, PMCID: PMC112596, DOI: 10.1128/jvi.73.7.5402-5410.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DivisionDendritic CellsDNA-Binding ProteinsFemaleHistocompatibility TestingHLA-A AntigensHLA-B AntigensHLA-C AntigensHumansImmunophenotypingInterferon-gammaInterleukin-4Intracellular FluidK562 CellsOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsAutologous dendritic cellsAutologous tumor cellsDendritic cellsHuman papillomavirus type 16Cervical cancerLymphoblastoid cell linesPapillomavirus type 16HPV 16CTL populationsT cellsType 16Autologous Epstein-Barr virus-transformed lymphoblastoid cell linesAnti-HLA class II antibodiesAutologous tumor target cellsAnti-HLA class ICytotoxic T lymphocyte responsesTwo-color flow cytometric analysisVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesT cell proliferative responsesTumor cellsPotential tumor-specific targetClass II antibodiesIntracellular cytokine expressionT lymphocyte responses