2024
Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma
McNamara B, Greenman M, Bellone S, Santin L, Demirkiran C, Mutlu L, Hartwich T, Yang-Hartwich Y, Ratner E, Schwartz P, Santin A. Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma. Gynecologic Oncology 2024, 189: 16-23. PMID: 38981151, DOI: 10.1016/j.ygyno.2024.07.002.Peer-Reviewed Original ResearchTargets trophoblast cell-surface antigen-2Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityPreclinical activityAntibody drug conjugatesOvarian cancerCell linesTumor cellsTrophoblast cell surface antigen 2Cell line-derived xenograft modelFlow cytometryCompared to tumor cellsEpithelial ovarian cancer cell linesOvarian cancer cell linesTumor cells in vitroOvarian cancer patientsPeripheral-blood lymphocytesEOC cell linesTumor growth suppressionAnnexin V-positiveGynecologic cancer mortalityIn vivo antitumor activityCells in vitroPrimary cell linesUnmet medical needTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancer
2023
The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expression
2017
Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo
Menderes G, Bonazzoli E, Bellone S, Black JD, Lopez S, Pettinella F, Masserdotti A, Zammataro L, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo. Medical Oncology 2017, 34: 91. PMID: 28397106, PMCID: PMC5896014, DOI: 10.1007/s12032-017-0956-8.Peer-Reviewed Original ResearchConceptsEpithelial ovarian carcinomaOvarian carcinoma xenograftsOvarian cancerOvarian carcinomaCarcinoma xenograftsPreclinical efficacyCell linesTumor cell linesHER2/neu expressionChemotherapy-resistant diseaseOvarian cancer cell linesAvailable treatment strategiesEfficacy of neratinibInhibits xenograft growthNovel therapeutic agentsPrimary tumor cell linesG0/G1 phaseCell cycle distributionCell signaling changesNeratinib treatmentCancer cell linesGynecologic malignanciesOverall survivalNeu expressionClinical trials
2015
Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery
Romani C, Cocco E, Bignotti E, Moratto D, Bugatti A, Todeschini P, Bandiera E, Tassi R, Zanotti L, Pecorelli S, Sartori E, Odicino FE, de Marco A, Santin AD, Ravaggi A, Mitola S. Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery. Oncotarget 2015, 6: 34617-34628. PMID: 26416446, PMCID: PMC4741477, DOI: 10.18632/oncotarget.5315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeoplasmAntibody AffinityAntineoplastic AgentsBlotting, WesternCell Line, TumorClaudin-3Drug CarriersDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansImmunoglobulin GMiceMice, SCIDMicroscopy, ConfocalMicroscopy, FluorescenceOvarian NeoplasmsReal-Time Polymerase Chain ReactionRNA, Small InterferingSurface Plasmon ResonanceTransfectionXenograft Model Antitumor AssaysConceptsClostridium perfringens enterotoxinTumor cellsActive anti-cancer compoundsHuman IgG1 Fc domainHuman ovarian cancer cell linesOvarian cancer cell linesOvarian cancer patientsOvarian carcinoma xenograftsOvarian cancer cellsIgG1 Fc domainCancer cell linesAggressive tumorsCancer patientsCarcinoma xenograftsOncological settingIgG1 antibodiesClaudin3Anti-cancer compoundsChimeric antibodyAntitumor efficacySelective drug deliveryPerfringens enterotoxinCancer cellsAntibodiesFc domainSolitomab, an EpCAM/CD3 bispecific antibody (BITE), is highly active against primary chemotherapy resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo
English D, Bellone S, Schwab C, Roque D, Chatterjee S, Ratner E, Schwartz P, Rutherford T, Santin A. Solitomab, an EpCAM/CD3 bispecific antibody (BITE), is highly active against primary chemotherapy resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo. Gynecologic Oncology 2015, 136: 401. DOI: 10.1016/j.ygyno.2014.11.041.Peer-Reviewed Original Research
2014
Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo
English DP, Bellone S, Schwab CL, Roque DM, Lopez S, Bortolomai I, Cocco E, Bonazzoli E, Chatterjee S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo. Cancer 2014, 121: 403-412. PMID: 25251053, PMCID: PMC4304922, DOI: 10.1002/cncr.29062.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, BispecificAntigens, NeoplasmCarcinoma, Ovarian EpithelialCD3 ComplexCell Adhesion MoleculesCell Line, TumorCytotoxicity, ImmunologicDrug Resistance, NeoplasmEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsT-LymphocytesConceptsOvarian cancer cell linesPeripheral blood lymphocytesTumor cellsCancer cell linesFlow cytometryBlood lymphocytesCell linesMalignant cellsChemotherapy-resistant cell linesChemotherapy-resistant ovarian cancerT cell-mediated killingT-cell activation markersCell-mediated cytotoxicity assayEpCAM expressionPrimary ovarian cancer cell linesFresh ovarian tumorsChemotherapy-resistant diseaseCD3 bispecific antibodyTumor-associated lymphocytesEpithelial ovarian carcinoma cell linesT cell cytotoxicityChromium release assaysFresh tumor cellsOvarian tumor cell linesOvarian tumor cellsSolitomab, an EpCAM/CD3 bispecific antibody (BiTE®), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo
English D, Schwab C, Roque D, Bellone S, Ratner E, Silasi D, Azodi M, Schwartz P, Rutherford T, Santin A. Solitomab, an EpCAM/CD3 bispecific antibody (BiTE®), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo. Gynecologic Oncology 2014, 133: 98. DOI: 10.1016/j.ygyno.2014.03.261.Peer-Reviewed Original Research
2012
Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer
Lal-Nag M, Battis M, Santin AD, Morin PJ. Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer. Oncogenesis 2012, 1: e33-e33. PMID: 23552466, PMCID: PMC3511677, DOI: 10.1038/oncsis.2012.32.Peer-Reviewed Original ResearchClostridium perfringens enterotoxinClaudin-6Claudin-3Ovarian cancer cell linesNovel receptorCell linesTight junction proteinsOvarian cell linesCancer cell linesOvarian cancerNovel functional receptorMouse modelCPE cytotoxicityClaudin-4Functional receptorsCancerEpithelial cell architecturePerfringens enterotoxinUCI 101Different cancersJunction proteinsReceptorsRapid cell lysisBinding assaysIntegral tight junction proteins
2011
Tissue 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 expressionHigh-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 assays
2010
High-grade, chemotherapy-resistant ovarian carcinomas overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody
Richter CE, Cocco E, Bellone S, Silasi DA, Rüttinger D, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. High-grade, chemotherapy-resistant ovarian carcinomas overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody. American Journal Of Obstetrics And Gynecology 2010, 203: 582.e1-582.e7. PMID: 20870202, PMCID: PMC2993821, DOI: 10.1016/j.ajog.2010.07.041.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmAntineoplastic AgentsBiomarkers, TumorCell Adhesion MoleculesCell Line, TumorDrug Resistance, NeoplasmFemaleFlow CytometryHumansImmunotherapyNeoplasm StagingOvarian NeoplasmsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSensitivity and SpecificityConceptsAntibody-dependent cell-mediated cytotoxicityComplement-dependent cytotoxicityReal-time polymerase chain reactionEpithelial cell adhesion moleculePolymerase chain reactionOvarian carcinomaInterleukin-2Cell adhesion moleculeFlow cytometryHighest messenger RNA expressionCell linesAdhesion moleculesCell-mediated cytotoxicityOvarian cancer cell linesEffective treatment optionChromium release assaysChain reactionMessenger RNA expressionCancer cell linesOvarian diseaseTreatment optionsOvarian cancerEpCAM expressionAnti-EpCAM antibodyRNA expressionClostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer
Cocco E, Casagrande F, Bellone S, Richter CE, Bellone M, Todeschini P, Holmberg JC, Fu HH, Montagna MK, Mor G, Schwartz PE, Arin-Silasi D, Azoudi M, Rutherford TJ, Abu-Khalaf M, Pecorelli S, Santin AD. Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer. BMC Cancer 2010, 10: 349. PMID: 20598131, PMCID: PMC2908101, DOI: 10.1186/1471-2407-10-349.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma, Clear CellAnimalsCarcinoma, PapillaryCarcinoma, Squamous CellChlorocebus aethiopsClaudin-3Claudin-4Clostridium perfringensCystadenocarcinoma, SerousDrug Resistance, NeoplasmEnterotoxinsFemaleFibroblastsFlow CytometryHumansMembrane ProteinsMiceMice, SCIDOvarian NeoplasmsPeptide FragmentsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSpheroids, CellularTissue DistributionTransplantation, HeterologousTumor Cells, CulturedUterine Cervical NeoplasmsVero CellsConceptsChemotherapy-resistant ovarian cancerClostridium perfringens enterotoxinOvarian cancerOvarian carcinoma cell linesClaudin-3Carcinoma cell linesNovel tumor-homing peptideCarboxy-terminal fragmentTumor cellsResistant ovarian cancer cell linesCell linesNew diagnostic tracersCPE peptideOvarian cancer cell linesResistant ovarian cancer cellsResistant ovarian carcinomaHuman ovarian cancerRelevant animal modelsOvarian tumor cellsOvarian cancer cellsChemotherapy-resistant ovarian cancer cellsHuman epithelial tumorsTime-dependent internalizationCancer cell linesBio-distribution studiesEpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201) in chemotherapy-resistant ovarian cancer cell lines.
Richter C, Cocco E, Bellone S, Casagrande F, Bellone M, Silasi D, Azodi M, Schwartz P, Rutherford T, Santin A. EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201) in chemotherapy-resistant ovarian cancer cell lines. Journal Of Clinical Oncology 2010, 28: e15524-e15524. DOI: 10.1200/jco.2010.28.15_suppl.e15524.Peer-Reviewed Original Research
2004
Increased levels of gangliosides in the plasma and ascitic fluid of patients with advanced ovarian cancer
Santin AD, Ravindranath MH, Bellone S, Muthugounder S, Palmieri M, O'Brien TJ, Roman J, Cannon MJ, Pecorelli S. Increased levels of gangliosides in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG An International Journal Of Obstetrics & Gynaecology 2004, 111: 613-618. PMID: 15198791, DOI: 10.1111/j.1471-0528.2004.00142.x.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsAdvanced ovarian cancerAdvanced ovarian cancer patientsNormal female controlsPrimary ovarian cancer cell linesOvarian cancer cell linesCancer patientsCancer cell linesOvarian cancerTotal gangliosidesFemale controlsAscitic fluidUterine carcinoma cell linesCell linesJohn Wayne Cancer InstituteAnti-tumor immune functionGanglioside levelsUterine cancer cell linesLipid-associated sialic acidTotal ganglioside levelsTime of surgeryDepartment of ObstetricsPrimary cervical cancerPrimary ovarian tumorsOvarian tumor cells
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
1996
Effects of cytokines combined with high‐dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule‐1 in human ovarian cancers
Santin A, Rose G, Hiserodt J, Fruehauf J, Eck L, Garcia R, Schranz V, Disaia P, Pecorelli S, Granger G. Effects of cytokines combined with high‐dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule‐1 in human ovarian cancers. International Journal Of Cancer 1996, 65: 688-694. PMID: 8598323, DOI: 10.1002/(sici)1097-0215(19960301)65:5<688::aid-ijc21>3.0.co;2-2.Peer-Reviewed Original ResearchConceptsMHC class 1TNF-alphaAntigen expressionIFN-gammaFresh tumorsOvarian cell linesTumor cellsIntercellular adhesion molecule-1Cell linesICAM-1 antigen expressionHuman ovarian cancer cell linesOvarian cancer cell linesMajor histocompatibility complex moleculesICAM-1 antigenCytokines TNF-alphaClass 1Adhesion molecule-1Human ovarian cancerHuman ovarian tumorsEffects of cytokinesHuman ovarian cell linesRemoval of cytokinesICAM-1 surfaceHistocompatibility complex moleculesCancer cell lines