2018
Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic options
2011
Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma
Bignotti E, Ravaggi A, Romani C, Falchetti M, Lonardi S, Facchetti F, Pecorelli S, Varughese J, Cocco E, Bellone S, Schwartz PE, Rutherford TJ, Santin AD. Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma. International Journal Of Gynecological Cancer 2011, 21: 1613-1621. PMID: 21892093, PMCID: PMC3233648, DOI: 10.1097/igc.0b013e318228f6da.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorComplement System ProteinsEndometrial NeoplasmsFemaleFlow CytometryHumansImmunization, PassiveImmunoglobulin GImmunohistochemistryRNA, MessengerConceptsEndometrial endometrioid carcinomaNormal endometrial controlsTrop-2 expressionEEC cell linesAntibody-dependent cellular cytotoxicityReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionEndometrioid carcinomaPolymerase chain reactionCellular cytotoxicityTrop-2Anti-Trop-2 antibodyCell linesTherapeutic agentsCr-release assaysTrop-2 overexpressionGrade 3 tumorsStandard treatment modalityChain reactionNovel therapeutic agentsCell surface markersEndometrial controlTreatment modalitiesPrimary cell linesEEC samplesTissue factor expression in ovarian cancer: implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor
Cocco E, Varughese J, Buza N, Bellone S, Lin KY, Bellone M, Todeschini P, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Carrara L, Tassi R, Pecorelli S, Lockwood CJ, Santin AD. Tissue factor expression in ovarian cancer: implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor. Clinical & Experimental Metastasis 2011, 28: 689-700. PMID: 21725665, PMCID: PMC3697933, DOI: 10.1007/s10585-011-9401-0.Peer-Reviewed Original ResearchConceptsOvarian cancer cell linesTissue factorCancer cell linesOvarian tumorsOvarian cancerCell linesOverexpression of CD59Targeting tissue factorClear cell histologyStandard treatment modalityExpression of TFEffect of complementNovel therapeutic agentsTissue factor expressionRNA-mediated knockdownEOC cell linesCell histologyOvarian diseaseΓ-immunoglobulinPrimary EOCTreatment modalitiesPhysiologic dosesInterleukin-2Undifferentiated tumorsCD59 expressionExpression 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 therapiesUterine 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
hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for immunotherapy of uterine serous papillary carcinoma
Cocco E, Hu Z, Richter CE, Bellone S, Casagrande F, Bellone M, Todeschini P, Krikun G, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Buza N, Pecorelli S, Lockwood CJ, Santin AD. hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for immunotherapy of uterine serous papillary carcinoma. British Journal Of Cancer 2010, 103: 812-819. PMID: 20700124, PMCID: PMC2966612, DOI: 10.1038/sj.bjc.6605760.Peer-Reviewed Original ResearchConceptsUSPC cell linesInterleukin-2Tissue factorTF expressionReal-time PCRFactor VIILow HER2/neu expressionCell linesLow dosesPrimary USPC cell linesDependent cell-mediated cytotoxicityUterine serous papillary carcinomaHER2/neu expressionTargeting tissue factorSerous papillary adenocarcinomaStandard treatment modalityCell-mediated cytotoxicityTreatment of patientsNormal endometrial cellsSerous papillary carcinomaNovel therapeutic agentsType II receptorAdenocarcinoma cell lineEndometrial cancerAggressive variantOverexpression 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
Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy
Bellone S, Siegel ER, Cocco E, Cargnelutti M, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy. International Journal Of Gynecological Cancer 2009, 19: 860-866. PMID: 19574774, DOI: 10.1111/igc.0b013e3181a8331f.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Clear CellAdenocarcinoma, MucinousAdultAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBlotting, WesternCarcinoma, PapillaryCell Adhesion MoleculesChemotherapy, AdjuvantCystadenocarcinoma, SerousDrug Resistance, NeoplasmEndometrial NeoplasmsEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansImmunoenzyme TechniquesMiddle AgedNeoplasm Recurrence, LocalOrganoplatinum CompoundsOvarian NeoplasmsOvaryPrognosisRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsRecurrent epithelial ovarian carcinomaEpithelial ovarian carcinomaNormal ovarian tissuesOvarian carcinoma cell linesOvarian carcinomaEpithelial cell adhesion moleculeEp-CAMCarcinoma cell linesCell adhesion moleculeOvarian tissueChemotherapy-resistant epithelial ovarian cancerFlow cytometryCell linesAdhesion moleculesEp-CAM overexpressionStandard treatment modalityCell adhesion molecule expressionOvarian carcinoma patientsEpithelial ovarian cancerPrimary ovarian carcinomasAdhesion molecule expressionSurface expressionAntibody-mediated therapyHuman monoclonal antibodyEpithelial cell adhesion molecule (EpCAM) expressionPotential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma
Santin A, Bellone S, El-Sahwi K, Buza N, Tavassoli F, Silasi D, Azodi M, Schwartz P, Rutherford T, Pecorelli S. Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma. Journal Of Clinical Oncology 2009, 27: e16502-e16502. DOI: 10.1200/jco.2009.27.15_suppl.e16502.Peer-Reviewed Original ResearchUterine serous papillary carcinomaPrimary USPC cell linesAntibody-dependent cellular cytotoxicityUSPC cell linesNormal endometrial cellsSerous papillary carcinomaComplement-dependent cytotoxicityHuman monoclonal antibodyEpithelial cell adhesion moleculeEndometrial cellsCell adhesion moleculePapillary carcinomaTherapeutic strategiesCell linesChromium release cytotoxicity assaysFlow cytometryEpCAM expressionMonoclonal antibodiesDependent cytotoxicityAdhesion moleculesRelease cytotoxicity assayStandard treatment modalityDependent cellular cytotoxicityUterine serous carcinomaAggressive biologic behavior
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
Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer.
Santin AD, Bellone S, Underwood LJ, O'Brien TJ, Ravaggi A, Pecorelli S, Cannon MJ. Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer. Minerva Obstetrics And Gynecology 2002, 54: 133-44. PMID: 12032451.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, NeoplasmCancer VaccinesChildClinical Trials as TopicCombined Modality TherapyDendritic CellsFemaleGPI-Linked ProteinsHumansImmunohistochemistryImmunotherapyKallikreinsMatrix Metalloproteinase 7Membrane ProteinsNeoplasm MetastasisOvarian NeoplasmsSerine EndopeptidasesT-Lymphocytes, CytotoxicTumor Cells, CulturedConceptsTumor antigensOvarian cancerChemotherapy-resistant ovarian cancerOvarian tumor-associated antigensDendritic cell-based immunotherapyTumor-specific immune responsesEffective tumor antigensTherapeutic DC vaccinationNovel immunotherapeutic strategiesStandard treatment modalityCell-based immunotherapyOvarian tumor antigenSpecific immune responseTumor-associated antigensPotential of DCDC vaccinationImmunotherapeutic strategiesDendritic cellsCancer vaccinationCancer patientsGynecologic oncologyTreatment modalitiesNatural adjuvantImmune responseAntigen preparations