2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
2015
Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients
Bellone S, Centritto F, Black J, Schwab C, English D, Cocco E, Lopez S, Bonazzoli E, Predolini F, Ferrari F, Silasi DA, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients. Gynecologic Oncology 2015, 138: 11-17. PMID: 25931171, PMCID: PMC4469551, DOI: 10.1016/j.ygyno.2015.04.027.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesCancer patientsPole tumorsT cellsHigher IFN-γ expressionLevels of CD8Endometrial cancer patientsTumor-specific CD4T cell responsesEndometrial cancer cellsIFN-γ expressionHelper armCTL responsesEndometrial cancerFavorable prognosisBetter prognosisEndometrial carcinomaLymphoid subsetsNaïve CD4T lymphocytesTumor extractsCD4CD8Immune systemCell responses
2012
Antigen-specific immunotherapy for ovarian cancer
Roque D, Santin A. Antigen-specific immunotherapy for ovarian cancer. 2012, 136-154. DOI: 10.2217/ebo.11.180.Peer-Reviewed Original ResearchOvarian cancer immunotherapyAntigen-specific immunotherapyTumor-associated antigensCancer immunotherapyOvarian tumor-associated antigensSpecific T cell responsesCritical immune checkpointsRegulatory T cellsT cell responsesOvarian cancer pathogenesisB7 family proteinsImmune checkpointsClinical trialsOvarian cancerT cellsImmune responseSuccessful therapyInhibitory pathwaysImmune evasionImmunotherapySpecific antigenHost defenseCancer pathogenesisAntigenTumors
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
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 reactionDefinition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme
Bondurant KL, Crew MD, Santin AD, O'Brien TJ, Cannon MJ. Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme. Clinical Cancer Research 2005, 11: 3446-3454. PMID: 15867247, DOI: 10.1158/1078-0432.ccr-04-2043.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicDendritic CellsFemaleHLA-A2 AntigenHumansImmunodominant EpitopesInterferon-gammaInterleukin-4K562 CellsKallikreinsMolecular Sequence DataOvarian NeoplasmsPeptide FragmentsProtein BindingSerine EndopeptidasesT-Lymphocytes, CytotoxicConceptsSerine protease stratum corneum chymotryptic enzymeOvarian tumor cellsHelper T-cell epitopesAntigen-specific CD4T cell responsesDendritic cellsHLA-A2.1T cell epitopesCTL responsesCell epitopesTumor cellsCTL epitopesStratum corneum chymotryptic enzymeCell responsesPeptide-loaded dendritic cellsTumor antigen-specific CD8Helper T cell responsesT helper cell epitopesAntigen-specific CD8Attractive target antigenLevel of lysisDominant CD8Multiple CD8Chymotryptic enzymeHLA-DRTherapeutic vaccines for cervical cancer: dendritic cell-based immunotherapy.
Santin AD, Bellone S, Roman JJ, Burnett A, Cannon MJ, Pecorelli S. Therapeutic vaccines for cervical cancer: dendritic cell-based immunotherapy. Current Pharmaceutical Design 2005, 11: 3485-500. PMID: 16248803, DOI: 10.2174/138161205774414565.Peer-Reviewed Original ResearchConceptsCervical cancer patientsT cell responsesDendritic cellsCervical cancerCancer patientsE7 oncoproteinsLate-stage cervical cancer patientsTumor-specific T-cell responsesImmune systemCell responsesPowerful antigen-presenting cellsDendritic cell-based immunotherapyPrimary T cell responsesCell-mediated immune responsesAutologous dendritic cellsTherapeutic HPV vaccinesTreatment-induced immunosuppressionPrimary radiation therapyHuman papillomavirus infectionAdvanced cervical cancerCell-based immunotherapyTumor-specific target antigensAntigen-presenting cellsImportant risk factorGold standard treatment
2003
Restoration of Tumor-Specific HLA Class I Restricted Cytotoxicity in Tumor Infiltrating Lymphocytes of Advanced Breast Cancer Patients by in vitro Stimulation with Tumor Antigen-Pulsed Autologous Dendritic Cells
Kass R, Bellone S, Palmieri M, Canè S, Bignotti E, Henry-Tillman R, Hutchins L, Cannon MJ, Klimberg S, Santin AD. Restoration of Tumor-Specific HLA Class I Restricted Cytotoxicity in Tumor Infiltrating Lymphocytes of Advanced Breast Cancer Patients by in vitro Stimulation with Tumor Antigen-Pulsed Autologous Dendritic Cells. Breast Cancer Research And Treatment 2003, 80: 275-285. PMID: 14503800, DOI: 10.1023/a:1024938215782.Peer-Reviewed Original ResearchConceptsPeripheral blood lymphocytesCytotoxic T lymphocytesTumor-specific cytotoxic T lymphocytesTumor-specific lytic activityAdvanced breast cancer patientsBreast cancer patientsCancer patientsInterleukin-2Breast cancerAnti-HLA class I mAbsNK-sensitive cell line K562Tumor-specific T-cell responsesChemotherapy-resistant breast cancerAdoptive T-cell immunotherapyAutologous dendritic cellsTh1 cytokine biasAutologous tumor cellsResistant breast cancerT cell responsesTumor-Infiltrating LymphocytesDendritic cell stimulationT cell populationsT-cell immunotherapyPotential of tumorHLA class I
2002
Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer
Cannon MJ, O’Brien T, Underwood LJ, Crew MD, Bondurant KL, Santin AD. Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer. Expert Review Of Anticancer Therapy 2002, 2: 97-105. PMID: 12113075, DOI: 10.1586/14737140.2.1.97.Peer-Reviewed Original ResearchConceptsDendritic cell-based immunotherapyCell-based immunotherapyPowerful antigen-presenting cellsPrimary T cell responsesDendritic cell vaccinationT cell responsesOvarian tumor antigenTumor-specific target antigensAntigen-presenting cellsTumor-specific antigensEffective immune responseCell vaccinationDendritic cellsMalignant diseaseOvarian cancerImmune responseTumor antigensTarget antigenImmunotherapyAntigenNovel targetVaccinationRecent recognitionCellsTumors
2000
Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells
SANTIN A, BELLONE S, RAVAGGI A, PECORELLI S, CANNON M, PARHAM G. Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells. Obstetrics And Gynecology 2000, 96: 422-430. DOI: 10.1097/00006250-200009000-00019.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerT lymphocyte responsesCytotoxic T lymphocytesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responseTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsPeptide-pulsed dendritic cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityInduction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells.
Santin A, Bellone S, Ravaggi A, Pecorelli S, Cannon M, Parham G. Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells. Obstetrics And Gynecology 2000, 96: 422-30. PMID: 10960637, DOI: 10.1016/s0029-7844(00)00916-9.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerPeptide-pulsed dendritic cellsT lymphocyte responsesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responsePeptide-pulsed autologous dendritic cellsTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityDevelopment and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Coke C, Pecorelli S, Cannon MJ, Parham GP. Development and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer. Gynecologic And Obstetric Investigation 2000, 49: 194-203. PMID: 10729762, DOI: 10.1159/000010246.Peer-Reviewed Original ResearchMeSH KeywordsAgedCD56 AntigenCD8-Positive T-LymphocytesCombined Modality TherapyDendritic CellsEndometrial NeoplasmsFemaleFlow CytometryHepatic ArteryHistocompatibility Antigens Class IHumansImmunophenotypingImmunotherapy, AdoptiveLiver NeoplasmsL-Lactate DehydrogenaseT-LymphocytesTomography, X-Ray ComputedUric AcidConceptsAutologous dendritic cellsDendritic cellsT cellsLiver metastasesEndometrial cancerAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingType 1 cytokine biasTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsLarge liver metastasesMetastatic endometrial cancerAutologous tumor cellsTumor-specific CD8T cell responsesEpstein-Barr virus-transformed lymphoblastoid cellsSerum uric acidIntracellular IFN-gammaBlood T cellsLactate dehydrogenaseT-cell immunotherapyLarge tumor massSerial time points