2011
Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. American Journal Of Obstetrics And Gynecology 2011, 205: 567.e1-567.e7. PMID: 21889762, PMCID: PMC3224189, DOI: 10.1016/j.ajog.2011.06.093.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntibodies, MonoclonalAntigens, NeoplasmBiomarkers, TumorCarcinoma, Squamous CellCell Adhesion MoleculesCell Line, TumorComplement System ProteinsDrug Resistance, NeoplasmDrug SynergismFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GInterleukin-2Killer Cells, NaturalReal-Time Polymerase Chain ReactionUterine Cervical NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityAnti-Trop-2 antibodyTrop-2 expressionReal-time polymerase chain reactionCell surface markersCervical cancerPolymerase chain reactionHighest messenger RNA expressionCell-dependent cytotoxicityCell-mediated cytotoxicityNovel treatment optionsChromium release assaysConventional treatment modalitiesChain reactionComplement-dependent cytotoxicityEffects of interleukinMessenger RNA expressionLevel of cytotoxicityCancer refractoryCervical carcinomaTreatment optionsTreatment modalitiesIL-2Normal cervixRelease assaysExpression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor
Cocco E, Varughese J, Buza N, Bellone S, Glasgow M, Bellone M, Todeschini P, Carrara L, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Lockwood CJ, Santin AD. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor. BMC Cancer 2011, 11: 263. PMID: 21693061, PMCID: PMC3141777, DOI: 10.1186/1471-2407-11-263.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCell Line, TumorComplement System ProteinsCytotoxicity Tests, ImmunologicDrug Screening Assays, AntitumorFemaleHuman papillomavirus 16Human papillomavirus 18HumansImmunoconjugatesImmunoglobulin GImmunotherapyInterleukin-2KeratinocytesMolecular Targeted TherapyNeoplasm ProteinsNeovascularization, PathologicPapillomavirus InfectionsRNA, MessengerRNA, NeoplasmThromboplastinUterine Cervical NeoplasmsConceptsCervical cancer cell linesPrimary cervical cancer cell linesCervical carcinoma cell linesCancer cell linesCervical cancerCarcinoma cell linesFactor VII/VIIaTissue factorUterine cervixCell linesImportant worldwide health problemTargeting tissue factorStandard treatment modalitySquamous cell carcinomaExpression of TFWorldwide health problemNovel therapeutic agentsNormal cervical keratinocytesAdenocarcinoma histologyBackgroundCervical cancerCancer refractoryRecurrent diseaseCell carcinomaTreatment modalitiesNovel therapiesHigh-grade, chemotherapy-resistant primary ovarian carcinoma cell lines overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Bellone M, Todeschini P, Carrara L, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. High-grade, chemotherapy-resistant primary ovarian carcinoma cell lines overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. Gynecologic Oncology 2011, 122: 171-177. PMID: 21453957, PMCID: PMC3104081, DOI: 10.1016/j.ygyno.2011.03.002.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCell Adhesion MoleculesCell Line, TumorDrug Resistance, NeoplasmFemaleFlow CytometryHumansImmunoglobulin GImmunohistochemistryInterleukin-2Killer Cells, NaturalMiddle AgedMolecular Targeted TherapyOvarian NeoplasmsRNA, MessengerConceptsAntibody-dependent cellular cytotoxicityOvarian cancer cell linesTrop-2 expressionAnti-Trop-2 antibodyChemotherapy-resistant ovarian cancerPrimary ovarian cancer cell linesCancer cell linesOvarian carcinoma cell linesInterleukin-2Cell surface markersCarcinoma cell linesOvarian cancerCell linesTrop-2Therapeutic agentsChemotherapy-resistant diseaseNovel therapeutic agentsEffect of serumOvarian diseaseControl antibodyHRS7Real-time PCRCellular cytotoxicityCarcinoma specimensRelease assaysUterine serous papillary carcinomas overexpress human trophoblast‐cell‐surface marker (trop‐2) and are highly sensitive to immunotherapy with hRS7, a humanized anti‐trop‐2 monoclonal antibody
Varughese J, Cocco E, Bellone S, de Leon M, Bellone M, Todeschini P, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Uterine serous papillary carcinomas overexpress human trophoblast‐cell‐surface marker (trop‐2) and are highly sensitive to immunotherapy with hRS7, a humanized anti‐trop‐2 monoclonal antibody. Cancer 2011, 117: 3163-3172. PMID: 21246534, PMCID: PMC3128671, DOI: 10.1002/cncr.25891.Peer-Reviewed Original ResearchConceptsUterine serous papillary carcinomaPrimary USPC cell linesUSPC cell linesAntibody-dependent cellular cytotoxicitySerous papillary carcinomaTrop-2 expressionReal-time polymerase chain reactionPolymerase chain reactionTrop-2Papillary carcinomaCell linesMonoclonal antibodiesChemotherapy-resistant variantsNatural killer cytotoxicityStandard treatment modalityUterine serous carcinomaComplement-dependent cytotoxicityNovel therapeutic strategiesNovel therapeutic agentsKiller cytotoxicityEndometrial cancerSerous carcinomaTreatment modalitiesControl antibodyHRS7
2010
Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201)
El-Sahwi K, Bellone S, Cocco E, Casagrande F, Bellone M, Abu-Khalaf M, Buza N, Tavassoli FA, Hui P, Rüttinger D, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201). Molecular Cancer Therapeutics 2010, 9: 57-66. PMID: 20053761, PMCID: PMC2806489, DOI: 10.1158/1535-7163.mct-09-0675.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCarcinoma, PapillaryCell Adhesion MoleculesCell Line, TumorCell MembraneCystadenocarcinoma, SerousDrug Resistance, NeoplasmDrug Screening Assays, AntitumorEpithelial Cell Adhesion MoleculeFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GImmunohistochemistryImmunotherapyInterleukin-2Killer Cells, NaturalMiddle AgedNeoplasm MetastasisRNA, MessengerUterine NeoplasmsConceptsUterine serous papillary carcinomaUSPC cell linesNormal endometrial cellsPrimary USPC cell linesAntibody-dependent cellular cytotoxicitySerous papillary carcinomaCellular cytotoxicityPapillary carcinomaCell linesFlow cytometryAdvanced/recurrentStandard treatment modalityCell-dependent cytotoxicityUterine serous carcinomaComplement-dependent cytotoxicitySurface expressionHuman monoclonal antibodyNovel therapeutic strategiesFresh frozen biopsiesHigh surface expressionEpithelial cell adhesion moleculeOverexpression of EpCAMParaffin-embedded tissuesMedian copy numberSerous carcinoma
2009
In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma
El-Sahwi K, Bellone S, Cocco E, Cargnelutti M, Casagrande F, Bellone M, Abu-Khalaf M, Buza N, Tavassoli FA, Hui P, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. British Journal Of Cancer 2009, 102: 134-143. PMID: 19920829, PMCID: PMC2813756, DOI: 10.1038/sj.bjc.6605448.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, PapillaryAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityCell Line, TumorComplement System ProteinsCytotoxicity, ImmunologicDimerizationDrug Screening Assays, AntitumorDrug SynergismFemaleHumansImmunoglobulin GIn Vitro TechniquesInterleukin-2Killer Cells, NaturalLymphocytesMiddle AgedReceptor, ErbB-2Signal TransductionTrastuzumabUterine NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityUSPC cell linesHER2/neu expressionComplement-dependent cytotoxicityStrong antibody-dependent cell-mediated cytotoxicitySerous papillary adenocarcinomaNeu expressionHER2/neuPapillary adenocarcinomaHigh HER2/neu expressionLow HER2/neu expressionCell linesH chromium release assaysPrimary USPC cell linesAdvanced/recurrentCombination of pertuzumabCell-mediated cytotoxicityHumanised monoclonal antibodyChromium release assaysC-erbB2 gene amplificationActivity of pertuzumabNew therapeutic agentsProliferation-based assaysType II receptorEndometrial cancer
2003
Selection of HER-2/neu-positive tumor cells in early stage cervical cancer: implications for Herceptin-mediated therapy
Bellone S, Palmieri M, Gokden M, Joshua J, Roman JJ, Pecorelli S, Cannon MJ, Santin AD. Selection of HER-2/neu-positive tumor cells in early stage cervical cancer: implications for Herceptin-mediated therapy. Gynecologic Oncology 2003, 91: 231-240. PMID: 14529687, DOI: 10.1016/s0090-8258(03)00460-8.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityEarly-stage cervical cancerStage cervical cancerCervical cancer cell linesCancer cell linesCervical cancerPrimary cell linesNeu expressionPrimary cervical cancer cell linesCell linesHER-2/neu expressionSite of recurrenceInhibition of proliferationEffector cellsMetastatic lesionsIL-2Primary treatmentTumor biopsiesCellular cytotoxicityHumanized mAbOriginal tumorRecurrent sitesLow dosesFlow cytometryLow expression
2002
Overexpression of HER-2/neu in uterine serous papillary cancer.
Santin AD, Bellone S, Gokden M, Palmieri M, Dunn D, Agha J, Roman JJ, Hutchins L, Pecorelli S, O'Brien T, Cannon MJ, Parham GP. Overexpression of HER-2/neu in uterine serous papillary cancer. Clinical Cancer Research 2002, 8: 1271-9. PMID: 12006548.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibodies, Monoclonal, Murine-DerivedAntineoplastic AgentsBreast NeoplasmsCell DivisionCystadenocarcinoma, PapillaryCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunohistochemistryInterleukin-2Killer Cells, NaturalMiddle AgedNeoplasm StagingOvarian NeoplasmsReceptor, ErbB-2RituximabTrastuzumabTumor Cells, CulturedUterine NeoplasmsConceptsUterine serous papillary carcinomaAntibody-dependent cellular cytotoxicityUSPC cell linesIntensity of expressionOvarian cancerPrimary USPC cell linesUterine serous papillary cancerCell linesFlow cytometryHigh-grade ovarian cancerOvarian cancer cell linesSerous papillary carcinomaCell proliferationComplement-dependent cytotoxicityComplement-mediated cytotoxicityAttractive therapeutic strategyHuman serum IgGCancer cell linesEndometrial cancerNatural killerAggressive variantEffector cellsSerum IgGPapillary cancerIL-2
2001
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
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 cervixIntrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma.
Clemons-Miller AR, Chatta GS, Hutchins L, Angtuaco EJ, Ravaggi A, Santin AD, Cannon MJ. Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma. Clinical Cancer Research 2001, 7: 917s-924s. PMID: 11300492.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmB-LymphocytesCD8-Positive T-LymphocytesCytokinesDendritic CellsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGp100 Melanoma AntigenHumansImmunotherapyImmunotherapy, AdoptiveIndiumInterferon-gammaInterleukin-2Interleukin-4Interleukin-6MART-1 AntigenMelanomaMembrane GlycoproteinsMeningeal NeoplasmsMiddle AgedMonophenol MonooxygenaseNeoplasm ProteinsProteinsReverse Transcriptase Polymerase Chain ReactionTime FactorsTissue DistributionT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Necrosis Factor-alphaConceptsTumor necrosis factor alphaNecrosis factor alphaNeurological symptomsLeptomeningeal melanomaFactor alphaLow-dose IL-2 administrationType 1 cytokine profileAutologous dendritic cellsIL-2 administrationRight carotid arteryIntra-arterial deliveryT-cell immunotherapyGreater lytic activityLoss of hearingCTL infusionCytokine profileAutologous EBVDendritic cellsRecurrent melanomaOmmaya reservoirSpecific CTLIL-6IL-4Specific lysisLower extremities
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 cervixInterleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Roman J, Parham G, Cannon M. Interleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes. Journal Of Virology 2000, 74: 4729-4737. PMID: 10775611, PMCID: PMC111995, DOI: 10.1128/jvi.74.10.4729-4737.2000.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCytokinesCytotoxicity, ImmunologicFemaleFlow CytometryHistocompatibility Antigens Class IHumansInterleukin-10Interleukin-2Lymphocyte ActivationMembrane GlycoproteinsPapillomaviridaePapillomavirus InfectionsPerforinPore Forming Cytotoxic ProteinsTh1 CellsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsIL-10IL-2Immunosuppressive cytokinesT lymphocytesSolid-phase anti-CD3 antibodyTumor necrosis factor alphaIntracellular perforin levelsTh1 cytokine secretionAutologous tumor cellsTime pointsTumor-specific CTLsTh1 cytokine productionCervical cancer patientsCytotoxic activityCytotoxic T lymphocytesNecrosis factor alphaT cell proliferationAnti-CD3 antibodyIFN-gamma expressionFluorescence-activated cell sorterGrowth factor betaIL-2 expressionLater time pointsAdoptive transfusionCD56 molecules
1996
Development and characterization of an interleukin-2–transduced human ovarian carcinoma tumor vaccine not expressing major histocompatibility complex molecules
Santin A, Ioli G, Hiserodt J, Manetta A, Pecorelli S, DiSaia P, Granger G. Development and characterization of an interleukin-2–transduced human ovarian carcinoma tumor vaccine not expressing major histocompatibility complex molecules. American Journal Of Obstetrics And Gynecology 1996, 174: 633-640. PMID: 8623798, DOI: 10.1016/s0002-9378(96)70441-6.Peer-Reviewed Original ResearchConceptsIL-2Interleukin-2Ovarian carcinoma cellsOvarian cancerAllogeneic peripheral blood lymphocytesAdvanced epithelial ovarian cancerBALB/c nude miceChromium-51 release assaysMajor histocompatibility complex class IAdvance ovarian cancerCarcinoma cellsHistocompatibility complex class IEpithelial ovarian cancerMajor histocompatibility complex moleculesPeripheral blood lymphocytesHuman ovarian carcinoma cell linesHuman ovarian carcinoma cellsOvarian carcinoma cell linesComplex class ICytokine interleukin-2Long-term cytotoxicHistocompatibility complex moleculesMonths of studyUCI-107Tumor vaccines