2024
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
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
2020
Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Bellone S, Buza N, Hui P, Lopez S, Perrone E, Manara P, Zammataro L, Altwerger G, Han C, Tymon-Rosario J, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Scientific Reports 2020, 10: 973. PMID: 31969666, PMCID: PMC6976591, DOI: 10.1038/s41598-020-58009-3.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaSacituzumab govitecanTrop-2 expressionAntibody-drug conjugatesCell surface markersXenograft modelTrop-2Adenocarcinoma/adenosquamous carcinomaAnti-Trop-2 antibodyCell linesWeekly intravenous administrationSignificant tumor growth inhibitionCervical cancer patientsPrimary cervical cancerStrong diffuse stainingPrimary cervical tumorsCervical cancer cell linesEpithelial solid tumorsReal-time polymerase chain reactionTumor growth inhibitionHuman placental tissuePositive cell linesNegative cell linesVivo antitumor activityCancer cell lines
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patients
2018
In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers
Altwerger G, Bonazzoli E, Bellone S, Egawa-Takata T, Menderes G, Pettinella F, Bianchi A, Riccio F, Feinberg J, Zammataro L, Han C, Yadav G, Dugan K, Morneault A, Ponte JF, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers. Molecular Cancer Therapeutics 2018, 17: molcanther.0930.2017. PMID: 29440294, PMCID: PMC5932245, DOI: 10.1158/1535-7163.mct-17-0930.Peer-Reviewed Original ResearchConceptsEndometrial cancerXenograft modelCell linesTumor cell linesPatient-derived xenograft modelsUterine cancer cell linesAggressive endometrial cancersEndometrial cancer deathsExpression of FRαPrimary USC cell linesRecurrent endometrial cancerReceptor alpha expressionUSC cell linesImpressive antitumor activityMol Cancer TherUSC patientsCancer cell linesMedian survivalCancer deathPDX modelsPreclinical dataUterine cancerComplete resolutionIMGN853Grade 3
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
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 cells
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 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 therapies
2010
Primary Cervical Carcinoma Cell Lines 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, Bellone M, Casagrande F, Todeschini P, Rüttinger D, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Primary Cervical Carcinoma Cell Lines Overexpress Epithelial Cell Adhesion Molecule (EpCAM) and Are Highly Sensitive to Immunotherapy With MT201, a Fully Human Monoclonal Anti-EpCAM Antibody. International Journal Of Gynecological Cancer 2010, 20: 1440-1447. PMID: 21370592, PMCID: PMC3701951, DOI: 10.1111/igc.0b013e3181fb18a1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, NeoplasmCarcinomaCell Adhesion MoleculesCell Culture TechniquesCell Line, TumorEpithelial Cell Adhesion MoleculeFemaleFlow CytometryGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunotherapyMiddle AgedTreatment OutcomeUterine Cervical NeoplasmsYoung AdultConceptsCervical carcinoma cell linesEpithelial cell adhesion moleculeComplement-dependent cytotoxicityCervical cancer cell linesInterleukin-2Real-time polymerase chain reactionCarcinoma cell linesCell adhesion moleculeCancer cell linesAggressive tumorsPolymerase chain reactionAdhesion moleculesPrimary cervical cancer cell linesCell linesRelease assaysFlow cytometryHighest messenger RNA expressionStandard salvage therapyCell adhesion molecule expressionEffective treatment optionAdhesion molecule expressionChain reactionHuman monoclonal antibodyMessenger RNA expressionEpithelial cell adhesion molecule (EpCAM) expressionHigh-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 expression