2024
Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer
McNamara B, Greenman M, Demirkiran C, Mutlu L, Hartwich T, Bellone S, Manavella D, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Santin A. Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer. Gynecologic Oncology 2024, 190: s36. DOI: 10.1016/j.ygyno.2024.07.058.Peer-Reviewed Original ResearchSacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer
Greenman M, Bellone S, Demirkiran C, Hartwich T, Santin A. Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer. Gynecologic Oncology Reports 2024, 54: 101459. PMID: 39108617, PMCID: PMC11300917, DOI: 10.1016/j.gore.2024.101459.Peer-Reviewed Original ResearchHigh grade serous ovarian cancerAntibody-drug conjugatesSerous ovarian cancerSacituzumab govitecanOvarian cancerTreatment optionsPlatinum-resistant ovarian cancer patientsDose-limiting toxicityOvarian cancer patientsNovel treatment optionsPartial responseRecurrent diseaseDose reductionCancer patientsClinical trialsBackground treatmentTargeted treatmentChemotherapyTreatmentCancerDoseDiseaseOptionsTrop2PatientsPreclinical 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 cancerRandomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Altwerger G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. BJC Reports 2024, 2: 43. PMID: 39516558, PMCID: PMC11523995, DOI: 10.1038/s44276-024-00067-5.Peer-Reviewed Original ResearchPre-treated ovarian cancerOverall survivalBev armsDose reductionOvarian cancerTaxane responseRandomized phase 2 trialRandomized phase II trialPaclitaxel-resistant diseaseResultsThirty-seven patientsTreated with paclitaxelPhase 2 trialBiweekly bevacizumabDays 1,8,15Taxane-sensitiveUpdate survivalProgression-freePeritoneal cancerDose modificationTaxane sensitivityPlatinum resistanceSubset analysisSubgroup analysisResponse ratePatientsPreclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer
McNamara B, Demirkiran C, Hartwich T, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecologic Oncology 2024, 183: 133-140. PMID: 38493021, DOI: 10.1016/j.ygyno.2024.01.028.Peer-Reviewed Original ResearchLow grade serous ovarian carcinomaWhole-exome-sequencingGain-of-function mutationsVS-4718Preclinical efficacyLow grade serous ovarian cancerSerous ovarian cancerControl-treated miceTumor growth inhibitionWild-type KRASLoss of heterozygosityDecreased p-ERKRAF/MEK inhibitionMedian survivalOvarian cancerRecurrence rateTherapeutic optionsOral gavageTumor growthTumor samplesIn vivo activityMAPK pathway genesRAF/MEK inhibitorsP-ERKEx vivo
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
2022
EP015/#546 In vitro and in vivo efficacy of trastuzumab deruxtecan (T-DXd) in epithelial ovarian cancer with HER2/NEU overexpression
Mutlu L, Manavella D, Bellone S, Santin A. EP015/#546 In vitro and in vivo efficacy of trastuzumab deruxtecan (T-DXd) in epithelial ovarian cancer with HER2/NEU overexpression. 2022, a54.2-a54. DOI: 10.1136/ijgc-2022-igcs.106.Peer-Reviewed Original Research
2019
51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer
Perrone E, Lopez S, Zeibek B, Bellone S, Zammataro L, Manzano A, Bonazzoli E, Manara P, Scambia G, Santin A. 51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer. International Journal Of Gynecological Cancer 2019, 29: a29. DOI: 10.1136/ijgc-2019-igcs.51.Peer-Reviewed Original ResearchEpithelial ovarian cancerTrop-2 expressionSacituzumab govitecanPrimary tumor cell linesEOC cell linesTrop-2EOC xenograftsOvarian cancerCell linesTumor cell linesAggressive epithelial ovarian cancerLethal gynecologic malignancyHigh ADCC activityGreater antitumor effectParaffin-embedded tumorsGynecologic malignanciesADCC activityOvarian tumorsPreclinical activityClinical trialsEpithelial tumorsSignificant bystander effectAntitumor effectsStrong stainingActive metaboliteWhole exome sequencing (WES) of primary, metastatic and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Zeybek B, Bonazzoli E, Lopez S, Han C, Altwerger G, Menderes G, Bellone S, Bianchi A, Ratner E, Schwartz P, Santin A. Whole exome sequencing (WES) of primary, metastatic and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Gynecologic Oncology 2019, 154: 62-63. DOI: 10.1016/j.ygyno.2019.04.148.Peer-Reviewed Original Research
2016
Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer
Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G, Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. Journal Of Clinical Investigation 2016, 126: 4157-4173. PMID: 27721235, PMCID: PMC5096908, DOI: 10.1172/jci87252.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErbB ReceptorsFemaleHeterograftsHumansIntercellular Adhesion Molecule-1Macrophage-1 AntigenMacrophagesMiceMice, NudeNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationOvarian NeoplasmsSpheroids, CellularVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsTumor-associated macrophagesOvarian cancerTranscoelomic metastasisTumor cellsICAM-1Mouse modelEpithelial ovarian cancerOvarian cancer growthOvarian cancer metastasisSpheroid formationOvarian cancer progressionVEGF/VEGFRTumor cell proliferationPharmacological blockadeMetastatic cancerColon cancerCancer growthMetastasisAntibody neutralizationTumor growthCancerClinical pathologyCancer metastasisCancer progressionΑMβ2 integrin
2008
Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer. Cancer 2008, 115: 800-811. PMID: 19117353, DOI: 10.1002/cncr.24048.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsPeptide-specific CTLsOvarian cancerCancer patientsHealthy donorsLymphocyte antigenEnzyme-linked immunosorbent spot-forming cell assayHuman cytotoxic T-lymphocyte responsesNatural killer-sensitive K562 cellsAnti-HLA class I monoclonal antibodiesImmunogenic peptidesPeptide-loaded target cellsType 1 cytokine profileAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesSpecific cytotoxic T lymphocytesClass I monoclonal antibodiesMonoclonal antibody stimulationPotential immunogenic peptidesDendritic cell immunotherapyAdvanced ovarian cancerCTL precursor frequenciesIntracellular cytokine expressionT lymphocyte responsesHuman lymphocyte antigenGeneration of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2008, 200: 75.e1-75.e10. PMID: 18976739, DOI: 10.1016/j.ajog.2008.08.014.Peer-Reviewed Original ResearchConceptsPeptide-specific cytotoxic T lymphocytesCytotoxic T lymphocytesHuman leukocyte antigenLeukocyte antigenOvarian cancerT lymphocytesHuman cytotoxic T-lymphocyte responsesCytotoxic T-lymphocyte precursor frequenciesNatural killer-sensitive targetsPeptide-loaded target cellsType 1 cytokine profileCytotoxic T lymphocyte responsesT lymphocyte precursor frequenciesPotential immunogenic peptidesAdvanced ovarian cancerClass I antibodiesIntracellular cytokine expressionT lymphocyte responsesPositive healthy donorsInterferon-gamma productionT lymphocyte populationsPeripheral blood leukocytesCytokine profileELISPOT assayCytokine expression
2004
Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer
Santin A, Bellone S, Palmieri M, Bossini B, Cane' S, Bignotti E, Roman J, Cannon M, Pecorelli S. Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. International Journal Of Gynecological Cancer 2004, 14: 64-75. DOI: 10.1136/ijgc-00009577-200401000-00008.Peer-Reviewed Original ResearchPeripheral blood lymphocytesAdvanced ovarian cancerAdvanced ovarian cancer patientsDendritic cellsOvarian cancer patientsOvarian cancerT cellsCancer patientsClass ILymphoblastoid cell linesTumor antigen-loaded dendritic cellsTumor lysate-pulsed dendritic cellsTumor-specific T-cell responsesAutologous ovarian cancer cellsAutologous tumor target cellsDC stimulationLysate-pulsed dendritic cellsType 1 cytokine biasAntigen-loaded dendritic cellsAnti-HLA class IAutologous Epstein-Barr virusSpecific human leukocyte antigenProfessional antigen presenting cellsAdoptive T-cell immunotherapyAutologous tumor cellsRestoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer
Santin AD, Bellone S, Palmieri M, Bossini B, Cane' S, Bignotti E, Roman JJ, Cannon MJ, Pecorelli S. Restoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. International Journal Of Gynecological Cancer 2004, 14: 64-75. PMID: 14764031, DOI: 10.1111/j.1048-891x.2004.014175.x.Peer-Reviewed Original ResearchConceptsPeripheral blood lymphocytesAdvanced ovarian cancerAdvanced ovarian cancer patientsDendritic cellsOvarian cancer patientsOvarian cancerT cellsCancer patientsClass ILymphoblastoid cell linesTumor antigen-loaded dendritic cellsTumor lysate-pulsed dendritic cellsTumor-specific T-cell responsesAutologous ovarian cancer cellsAutologous tumor target cellsDC stimulationLysate-pulsed dendritic cellsType 1 cytokine biasAntigen-loaded dendritic cellsAnti-HLA class IAutologous Epstein-Barr virusIFN-gamma-positive cellsSpecific human leukocyte antigenProfessional antigen presenting cellsAdoptive T-cell immunotherapy
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 preparationsInduction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer
Santin AD, Bellone S, Ravaggi A, Roman JJ, Pecorelli S, Parham GP, Cannon MJ. Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer. British Journal Of Cancer 2002, 86: 151-157. PMID: 11857027, PMCID: PMC2746546, DOI: 10.1038/sj.bjc.6600026.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsUterine serous papillary cancerAutologous dendritic cellsT cellsPatient 1Patient 3Tumor cellsDendritic cellsPapillary cancerOvarian cancerAutologous tumor target cellsTumor lysate-pulsed DCsAnti-HLA class IUterine serous papillary carcinomaColor flow cytometric analysisCancer-specific CD8Cisplatinum-based chemotherapyLumboaortic lymph nodesPapillary cancer patientsTumor-specific toleranceTumor-specific CD8Intracellular cytokine expressionHigh-grade ovarian cancerT lymphocyte responsesStrong cytolytic activity
2001
Increased levels of interleukin-10 and transforming growth factor-β in the plasma and ascitic fluid of patients with advanced ovarian cancer
Santin A, Bellone S, Ravaggi A, Roman J, Smith C, Pecorelli S, Cannon M, Parham G. Increased levels of interleukin-10 and transforming growth factor-β in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG An International Journal Of Obstetrics & Gynaecology 2001, 108: 804-808. DOI: 10.1016/s0306-5456(00)00206-0.Peer-Reviewed Original ResearchOvarian cancer patientsAdvanced ovarian cancerIL-10Cancer patientsOvarian cancerAscitic fluidPlasma levelsPeritoneal fluidAdvanced ovarian cancer patientsElevated TGF-β levelsImmunosuppressive cytokine IL-10Anti-tumor immune functionDetectable IL-10Cytokine IL-10TGF-β levelsTime of surgeryDepartment of ObstetricsPlasma samplesNormal female controlsSensitive enzyme-linked immunosorbentEnzyme-linked immunosorbentTGF-β releaseImmunosuppressive cytokinesInterleukin-10Normal control plasma samplesIncreased levels of interleukin‐10 and transforming growth factor‐β in the plasma and ascitic fluid of patients with advanced ovarian cancer
Santin A, Bellone S, Ravaggi A, Roman J, Smith C, Pecorelli S, Cannon M, Parham G. Increased levels of interleukin‐10 and transforming growth factor‐β in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG An International Journal Of Obstetrics & Gynaecology 2001, 108: 804-808. PMID: 11510703, DOI: 10.1111/j.1471-0528.2001.00206.x.Peer-Reviewed Original ResearchConceptsOvarian cancer patientsAdvanced ovarian cancerIL-10Cancer patientsOvarian cancerAscitic fluidPlasma levelsPeritoneal fluidAdvanced ovarian cancer patientsElevated TGF-beta levelsImmunosuppressive cytokine IL-10Anti-tumor immune functionDetectable IL-10TGF-beta levelsCytokine IL-10Time of surgeryDepartment of ObstetricsTGF-beta releasePlasma samplesNormal female controlsSensitive enzyme-linked immunosorbentEnzyme-linked immunosorbentImmunosuppressive cytokinesInterleukin-10Prospective studyPhenotypic 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 markers