2020
Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer
Perrone E, Lopez S, Zeybek B, Bellone S, Bonazzoli E, Pelligra S, Zammataro L, Manzano A, Manara P, Bianchi A, Buza N, Tymon-Rosario J, Altwerger G, Han C, Menderes G, Ratner E, Silasi DA, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer. Frontiers In Oncology 2020, 10: 118. PMID: 32117765, PMCID: PMC7028697, DOI: 10.3389/fonc.2020.00118.Peer-Reviewed Original ResearchTrop-2 expressionEOC cell linesSacituzumab govitecanEpithelial ovarian cancerPrimary tumor cell linesPreclinical activityTrop-2EOC xenograftsOvarian cancerTrophoblast cell surface antigen 2Cell linesActive metaboliteTumor cell linesImpressive anti-tumor activityCell surface antigen 2Lethal gynecologic malignancyHigh ADCC activityAnti-tumor activityParaffin-embedded tumorsSignificant bystander killingGynecologic malignanciesADCC activityEOC tissuesOvarian tumorsClinical trialsSacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo
Perrone E, Manara P, Lopez S, Bellone S, Bonazzoli E, Manzano A, Zammataro L, Bianchi A, Zeybek B, Buza N, Tymon‐Rosario J, Altwerger G, Han C, Menderes G, Huang GS, Ratner E, Silasi D, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Sacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo. Molecular Oncology 2020, 14: 645-656. PMID: 31891442, PMCID: PMC7053235, DOI: 10.1002/1878-0261.12627.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmAntineoplastic AgentsCamptothecinCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorCell SurvivalEndometrial NeoplasmsFemaleHumansImmunoconjugatesImmunohistochemistryIrinotecanMiceMice, SCIDTissue Array AnalysisXenograft Model Antitumor AssaysConceptsAntibody-dependent cell cytotoxicityCell surface antigen 2EC cell linesSacituzumab govitecanTrop-2 expressionPrimary tumor cell linesTrop-2Xenograft modelAntigen 2Cell linesTumor cell linesCommon gynecologic malignancyFuture clinical trialsChromium release assaysParaffin-embedded tumorsTumor growth inhibitionSignificant bystander killingEC xenograftsGynecologic malignanciesEndometrial cancerEndometrial adenocarcinomaEndometrioid carcinoma tissuesPreclinical activityControl antibodyClinical trials
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 trialsDual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells
Cocco E, Deng Y, Shapiro EM, Bortolomai I, Lopez S, Lin K, Bellone S, Cui J, Menderes G, Black JD, Schwab CL, Bonazzoli E, Yang F, Predolini F, Zammataro L, Altwerger G, de Haydu C, Clark M, Alvarenga J, Ratner E, Azodi M, Silasi DA, Schwartz PE, Litkouhi B, Saltzman WM, Santin AD. Dual-Targeting Nanoparticles for In Vivo Delivery of Suicide Genes to Chemotherapy-Resistant Ovarian Cancer Cells. Molecular Cancer Therapeutics 2017, 16: 323-333. PMID: 27956521, PMCID: PMC5292071, DOI: 10.1158/1535-7163.mct-16-0501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalDisease Models, AnimalDrug CarriersDrug Delivery SystemsDrug Resistance, NeoplasmEnterotoxinsFemaleGene ExpressionGene Transfer TechniquesGenes, Transgenic, SuicideGenetic TherapyHumansMiceNanoparticlesOvarian NeoplasmsPromoter Regions, GeneticTumor BurdenXenograft Model Antitumor AssaysConceptsOvarian cancer cellsClostridium perfringens enterotoxinChemotherapy-resistant ovarian cancer cellsIntraperitoneal injectionCancer cellsMultiple intraperitoneal injectionsOvarian cancer xenograftsOvarian tumor cell linesLethal gynecologic cancerTumor-bearing miceOvarian cancer cell deathVivo biodistribution studiesGene therapySuicide gene therapyGynecologic cancerCancer xenograftsOvarian cancerCancer cell deathTherapeutic approachesControl nanoparticlesTumor growthTumor cell linesClaudin-3Biodistribution studiesTumor cells
2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors