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 need
2023
Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, 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 with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
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
2015
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
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 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
2009
Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines
Bellone S, El-Sahwi K, Cocco E, Casagrande F, Cargnelutti M, Palmieri M, Bignotti E, Romani C, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines. Journal Of Virology 2009, 83: 6779-6789. PMID: 19386711, PMCID: PMC2698533, DOI: 10.1128/jvi.02443-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCancer VaccinesCapsid ProteinsCell Line, TumorDendritic CellsFemaleGene Expression ProfilingHuman papillomavirus 16HumansMiddle AgedOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsRepressor ProteinsRNA, ViralT-Lymphocytes, CytotoxicUterine Cervical NeoplasmsYoung AdultConceptsCervical cancer patientsCytotoxic T lymphocytesAutologous tumor cellsCancer patientsDendritic cellsT lymphocytesL1 VLPsCervical cancerTumor cellsE7 RNADendritic cell-based therapeutic vaccineE7-specific cytotoxic T lymphocytesHPV-16 positive cervical cancerCell-mediated immune responsesExpression levelsAutologous dendritic cellsHPV-16 VLPPromising prophylactic vaccineE7-specific CD8Human papillomavirus infectionT lymphocyte responsesStrong cytolytic activityTreatment of patientsPeripheral blood lymphocytesPrimary cervical tumors
2002
Induction 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
Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells.
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman JJ, Jayaprabhu S, Pecorelli S, Parham GP, Cannon MJ. Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells. Clinical Cancer Research 2001, 7: 804s-810s. PMID: 11300476.Peer-Reviewed Original ResearchMeSH KeywordsCD56 AntigenCD8-Positive T-LymphocytesCell LineDendritic CellsDNA-Binding ProteinsFemaleFlow CytometryHLA-A2 AntigenHumansImmunotherapyInterferon-gammaMembrane GlycoproteinsOncogene Proteins, ViralPapillomavirus E7 ProteinsPerforinPhenotypePore Forming Cytotoxic ProteinsTime FactorsT-Lymphocytes, CytotoxicTumor Cells, CulturedUterine Cervical NeoplasmsConceptsAntigen-specific CTL responsesE7-specific CD8Dendritic cellsTumor target cellsHPV 16CTL responsesHLA-A2Lymphoblastoid cell linesCD56 expressionTumor cellsHealthy individualsType 1 cytokine profileAnti-HLA class IHLA-A2 monoclonal antibodyAutologous dendritic cellsE7-specific CTLExpression of CD56Subset of CD8Human papillomavirus infectionTarget cellsImportant risk factorHigh cytolytic activityCervical cancer cell linesIntracellular perforin expressionCell lines
2000
In vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G. In vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2000, 183: 601-609. PMID: 10992180, DOI: 10.1067/mob.2000.107097.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsCytotoxic T lymphocytesDendritic cellsAntigen class IT lymphocytesOvarian cancerTumor cellsAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor-specific cytotoxic T-cell responseAutologous ovarian cancer cellsAutologous ovarian tumor cellsHuman leukocyte antigen (HLA) class IAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesClass I monoclonal antibodiesCytotoxic T cell responsesVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesClass IHuman lymphocyte antigen class IAutologous dendritic cellsHigh cytotoxic activityInduction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells
SANTIN A, BELLONE S, RAVAGGI A, PECORELLI S, CANNON M, PARHAM G. Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells. Obstetrics And Gynecology 2000, 96: 422-430. DOI: 10.1097/00006250-200009000-00019.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerT lymphocyte responsesCytotoxic T lymphocytesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responseTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsPeptide-pulsed dendritic cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityInduction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells.
Santin A, Bellone S, Ravaggi A, Pecorelli S, Cannon M, Parham G. Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells. Obstetrics And Gynecology 2000, 96: 422-30. PMID: 10960637, DOI: 10.1016/s0029-7844(00)00916-9.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerPeptide-pulsed dendritic cellsT lymphocyte responsesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responsePeptide-pulsed autologous dendritic cellsTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityDevelopment, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix.
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Korourian S, Pecorelli S, Cannon MJ, Parham GP. Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix. European Journal Of Gynaecological Oncology 2000, 21: 17-23. PMID: 10726612.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsAutologous dendritic cellsDendritic cellsT cellsMetastatic diseaseUterine cervixAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsTumor cellsIntracellular cytokine productionAutologous tumor cellsExtensive metastatic diseaseInvasive cervical cancerTumor-specific CTLsIntracellular cytokine expressionEpstein-Barr virus-transformed lymphoblastoid cellsBlood mononuclear cellsTreatment of patientsBlood T cellsCytotoxic T cellsPeripheral blood lymphocytes