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
Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer. Cancer 2008, 115: 800-811. PMID: 19117353, DOI: 10.1002/cncr.24048.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsPeptide-specific CTLsOvarian cancerCancer patientsHealthy donorsLymphocyte antigenEnzyme-linked immunosorbent spot-forming cell assayHuman cytotoxic T-lymphocyte responsesNatural killer-sensitive K562 cellsAnti-HLA class I monoclonal antibodiesImmunogenic peptidesPeptide-loaded target cellsType 1 cytokine profileAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesSpecific cytotoxic T lymphocytesClass I monoclonal antibodiesMonoclonal antibody stimulationPotential immunogenic peptidesDendritic cell immunotherapyAdvanced ovarian cancerCTL precursor frequenciesIntracellular cytokine expressionT lymphocyte responsesHuman lymphocyte antigenGeneration of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2008, 200: 75.e1-75.e10. PMID: 18976739, DOI: 10.1016/j.ajog.2008.08.014.Peer-Reviewed Original ResearchConceptsPeptide-specific cytotoxic T lymphocytesCytotoxic T lymphocytesHuman leukocyte antigenLeukocyte antigenOvarian cancerT lymphocytesHuman cytotoxic T-lymphocyte responsesCytotoxic T-lymphocyte precursor frequenciesNatural killer-sensitive targetsPeptide-loaded target cellsType 1 cytokine profileCytotoxic T lymphocyte responsesT lymphocyte precursor frequenciesPotential immunogenic peptidesAdvanced ovarian cancerClass I antibodiesIntracellular cytokine expressionT lymphocyte responsesPositive healthy donorsInterferon-gamma productionT lymphocyte populationsPeripheral blood leukocytesCytokine profileELISPOT assayCytokine expression
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 response
2005
Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy
Santin AD, Zhan F, Cane' S, Bellone S, Palmieri M, Thomas M, Burnett A, Roman JJ, Cannon MJ, Shaughnessy J, Pecorelli S. Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. British Journal Of Cancer 2005, 92: 1561-1573. PMID: 15785748, PMCID: PMC2362016, DOI: 10.1038/sj.bjc.6602480.Peer-Reviewed Original ResearchConceptsUterine serous papillary cancerNormal endometrial cellsEndometrial cancerAggressive variantClaudin-4Normal endometrial epithelial cellsUterine serous papillary carcinomaAdhesion moleculesNovel therapeutic markerCommon gynecologic tumorsSerous papillary carcinomaParaffin-embedded specimensEndometrial epithelial cellsL1 cell adhesion moleculeType-specific therapiesRas homolog gene familyQuantitative RT-PCRScalar dosesGynecologic tumorsPapillary cancerEndometrial cellsInterleukin-6Cell adhesion moleculeNovel molecular markersPapillary carcinoma
2004
Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling
Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Gokden M, Roman JJ, O'Brien TJ, Tian E, Cannon MJ, Shaughnessy J, Pecorelli S. Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling. British Journal Of Cancer 2004, 90: 1814-1824. PMID: 15208622, PMCID: PMC2409747, DOI: 10.1038/sj.bjc.6601791.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCarcinoma, PapillaryCells, CulturedCystadenocarcinoma, SerousDiagnosis, DifferentialFemaleFlow CytometryGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiddle AgedOligonucleotide Array Sequence AnalysisOvarian NeoplasmsReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionUterine NeoplasmsConceptsUterine serous papillary carcinomaGene expressionOverexpressed genesSerous papillary carcinomaGene expression fingerprintGene expression profilingHuman genesC-erbB2 geneExpression fingerprintsMolecular basisExpression profilingPapillary carcinomaOligonucleotide microarraysExpression productsQuantitative RT-PCRGenesClinical tissue samplesProbe setsTwo-fold differenceMore effective treatment modalitiesEffective treatment modalitySerous papillary tumorsPlasminogen activator inhibitorDifferent biological behaviorDevelopment of novelRestoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer
Santin AD, Bellone S, Palmieri M, Bossini B, Cane' S, Bignotti E, Roman JJ, Cannon MJ, Pecorelli S. Restoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. International Journal Of Gynecological Cancer 2004, 14: 64-75. PMID: 14764031, DOI: 10.1111/j.1048-891x.2004.014175.x.Peer-Reviewed Original ResearchConceptsPeripheral blood lymphocytesAdvanced ovarian cancerAdvanced ovarian cancer patientsDendritic cellsOvarian cancer patientsOvarian cancerT cellsCancer patientsClass ILymphoblastoid cell linesTumor antigen-loaded dendritic cellsTumor lysate-pulsed dendritic cellsTumor-specific T-cell responsesAutologous ovarian cancer cellsAutologous tumor target cellsDC stimulationLysate-pulsed dendritic cellsType 1 cytokine biasAntigen-loaded dendritic cellsAnti-HLA class IAutologous Epstein-Barr virusIFN-gamma-positive cellsSpecific human leukocyte antigenProfessional antigen presenting cellsAdoptive T-cell immunotherapy
2003
Influence of Allogeneic Blood Transfusion on Clinical Outcome during Radiotherapy for Cancer of the Uterine Cervix
Santin AD, Bellone S, Parrish RS, Coke C, Dunn D, Roman J, Theus JW, Cannon MJ, Parham GP, Pecorelli S. Influence of Allogeneic Blood Transfusion on Clinical Outcome during Radiotherapy for Cancer of the Uterine Cervix. Gynecologic And Obstetric Investigation 2003, 56: 28-34. PMID: 12867765, DOI: 10.1159/000072328.Peer-Reviewed Original ResearchConceptsAllogeneic blood transfusionStage IIB patientsStage III patientsBlood transfusionRadiation treatmentCervical cancerRisk ratioIndependent variable predictivePrimary radiation treatmentRoutine blood transfusionProspective Randomized StudyCervical cancer patientsOnset of treatmentDuration of treatmentTotal radiation doseUntransfused groupException of hemoglobinRandomized studyClinical outcomesUterine cervixImmune suppressionCervical carcinomaCancer patientsDistribution of ageDiminished survival
2001
Increased levels of interleukin‐10 and transforming growth factor‐β in the plasma and ascitic fluid of patients with advanced ovarian cancer
Santin A, Bellone S, Ravaggi A, Roman J, Smith C, Pecorelli S, Cannon M, Parham G. Increased levels of interleukin‐10 and transforming growth factor‐β in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG An International Journal Of Obstetrics & Gynaecology 2001, 108: 804-808. PMID: 11510703, DOI: 10.1111/j.1471-0528.2001.00206.x.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsAdvanced ovarian cancerIL-10Cancer patientsOvarian cancerAscitic fluidPlasma levelsPeritoneal fluidAdvanced ovarian cancer patientsElevated TGF-beta levelsImmunosuppressive cytokine IL-10Anti-tumor immune functionDetectable IL-10TGF-beta levelsCytokine IL-10Time of surgeryDepartment of ObstetricsTGF-beta releasePlasma samplesNormal female controlsSensitive enzyme-linked immunosorbentEnzyme-linked immunosorbentImmunosuppressive cytokinesInterleukin-10Prospective studyPhenotypic and Functional Analysis of Tumor-Infiltrating Lymphocytes Compared with Tumor-Associated Lymphocytes from Ascitic Fluid and Peripheral Blood Lymphocytes in Patients with Advanced Ovarian Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman JJ, Smith CV, Pecorelli S, Radominska-Pandya A, Cannon MJ, Parham GP. Phenotypic and Functional Analysis of Tumor-Infiltrating Lymphocytes Compared with Tumor-Associated Lymphocytes from Ascitic Fluid and Peripheral Blood Lymphocytes in Patients with Advanced Ovarian Cancer. Gynecologic And Obstetric Investigation 2001, 51: 254-261. PMID: 11408737, DOI: 10.1159/000058060.Peer-Reviewed Original ResearchConceptsTumor-associated lymphocytesTumor-infiltrating lymphocytesPeripheral blood lymphocytesAdvanced ovarian cancerType 1 cytokinesT cellsBlood lymphocytesOvarian cancerAscitic fluidAntigen-experienced T lymphocytesActivation markers HLA-DREarly activation markers CD25Markers HLA-DRType 2 cytokinesActivation markers CD25Major leukocyte populationsIL-2 pathwayIL-2 receptorFunction of lymphocytesIL-2 productionLow surface expressionLymphocyte subsetsHigher proportionHLA-DRActivation markersTumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix
Santin A, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G, Hermonat P. Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix. Gynecologic Oncology 2001, 81: 424-432. PMID: 11371133, DOI: 10.1006/gyno.2001.6200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedCarcinoma, Squamous CellCD4-CD8 RatioCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesFemaleHLA-DR AntigensHumansImmunophenotypingInterferon-gammaInterleukin-2Interleukin-4Lymph NodesLymphocytesLymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingReceptors, Interleukin-2Th1 CellsTh2 CellsUterine Cervical NeoplasmsConceptsType 1 cytokinesLymph nodesPeripheral bloodT cellsTumor tissueLymphocyte subsetsStage IB-IIA cervical cancerAntigen-experienced T lymphocytesIB-IIA cervical cancerTumor draining lymph nodeActivation markers HLA-DREarly activation markers CD25Draining Lymph NodesMarkers HLA-DRType 2 cytokinesCervical cancer patientsRegional lymph nodesActivation markers CD25Tumor-Infiltrating LymphocytesMajor leukocyte populationsFunction of lymphocytesCervical tumor tissuesDifferent anatomical sitesHLA-DRUterine cervix
2000
Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix
Santin A, Hermonat P, Ravaggi A, Bellone S, Roman J, Pecorelli S, Cannon M, Parham G. Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix. International Journal Of Radiation Oncology • Biology • Physics 2000, 48: 997-1006. PMID: 11072156, DOI: 10.1016/s0360-3016(00)00769-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsCisplatinCombined Modality TherapyFemaleHumansImmunity, CellularInterferon-gammaInterleukin-2Killer Cells, NaturalLymphocyte ActivationLymphocyte SubsetsMembrane GlycoproteinsMiddle AgedPerforinPore Forming Cytotoxic ProteinsProspective StudiesReceptors, Interleukin-2Uterine Cervical NeoplasmsConceptsT cellsIL-2Lymphoblast transformationRadiation therapyImmune functionNatural killer cytotoxic activityCD25-positive lymphocytesRadiation-induced immunosuppressionPercentage of CD8Advanced cervical cancerT cell numbersNatural killer cellsT cell subsetsActivation markers CD25C-RTMean absolute numberB cell numbersK562 cellsCisplatinum administrationConcurrent cisplatinumLymphocyte subsetsNK cellsConcurrent administrationKiller cellsUterine cervixIn vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G. In vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2000, 183: 601-609. PMID: 10992180, DOI: 10.1067/mob.2000.107097.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsCytotoxic T lymphocytesDendritic cellsAntigen class IT lymphocytesOvarian cancerTumor cellsAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor-specific cytotoxic T-cell responseAutologous ovarian cancer cellsAutologous ovarian tumor cellsHuman leukocyte antigen (HLA) class IAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesClass I monoclonal antibodiesCytotoxic T cell responsesVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesClass IHuman lymphocyte antigen class IAutologous dendritic cellsHigh cytotoxic 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