2018
Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement
Bellone S, Buza N, Choi J, Zammataro L, Gay L, Elvin J, Rimm DL, Liu Y, Ratner E, Schwartz PE, Santin AD. Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clinical Cancer Research 2018, 24: 3282-3291. PMID: 29351920, PMCID: PMC6050068, DOI: 10.1158/1078-0432.ccr-17-1805.Peer-Reviewed Original ResearchMeSH KeywordsAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyComputational BiologyDrug Resistance, NeoplasmExome SequencingFemaleGene RearrangementHLA AntigensHumansMolecular Targeted TherapyMutationOvarian NeoplasmsPositron Emission Tomography Computed TomographyProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceRetreatmentT-LymphocytesTreatment OutcomeConceptsImmune checkpoint inhibitor pembrolizumabCheckpoint inhibitor pembrolizumabComplete clinical responseClinical responsePD-L1Ovarian carcinomaAberrant PD-L1 expressionPD-L1 surface expressionAnti-PD1 inhibitorsPD-L1 expressionRemarkable clinical responsesHigh-grade ovarian carcinomaStandard treatment modalityAlternative therapeutic optionClear cell featuresNovel treatment optionsSignificant side effectsT-cell lymphocytesWhole exome sequencing techniqueClin Cancer ResMetastatic human tumorsRecurrent diseaseComplete responseHeavy infiltrationTherapeutic options
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
2008
A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells
Wang X, Santin AD, Bellone S, Gupta S, Nakagawa M. A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells. Cancer Immunology, Immunotherapy 2008, 58: 301-308. PMID: 18446336, PMCID: PMC2782377, DOI: 10.1007/s00262-008-0525-2.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen PresentationCancer VaccinesCD4 AntigensDendritic CellsDose-Response Relationship, DrugEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHuman papillomavirus 16Human papillomavirus 18HumansMolecular Sequence DataNeoplasm StagingOncogene Proteins, ViralPapillomavirus E7 ProteinsSignal TransductionT-LymphocytesUterine Cervical NeoplasmsConceptsT cell epitopesCD4 T cell epitopesT cell responsesT cell clonesHPV 16T cell linesDose escalation phase I clinical trialPeripheral blood mononuclear cellsE7 proteinPositive T-cell responsesPhase I clinical trialAutologous mature DCDendritic cell vaccinationIIA cervical cancerCervical cancer patientsIFN-γ secretionBlood mononuclear cellsHuman papillomavirus type 16Papillomavirus type 16Cell vaccinationStage IBDendritic cellsMature DCsCervical cancerELISPOT assay
2005
HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities
Santin AD, Bellone S, Palmieri M, Ravaggi A, Romani C, Tassi R, Roman JJ, Burnett A, Pecorelli S, Cannon MJ. HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecologic Oncology 2005, 100: 469-478. PMID: 16249018, DOI: 10.1016/j.ygyno.2005.09.040.Peer-Reviewed Original ResearchConceptsCervical cancer patientsStandard treatment modalityAutologous dendritic cellsT cell responsesDendritic cellsCancer patientsTreatment modalitiesHPV16/18 E7Clinical responseIFN-gammaAutologous monocyte-derived dendritic cellsE7 oncoproteinsLate-stage cervical cancer patientsCell responsesMonocyte-derived dendritic cellsHuman recombinant interleukin-2Active vaccination strategiesHPV18 E7 oncoproteinLimited tumor burdenTreatment-induced immunosuppressionAutologous tumor cellsDendritic cell vaccinationObjective clinical responsesEarly-stage diseaseType hypersensitivity reaction
2003
Restoration of Tumor-Specific HLA Class I Restricted Cytotoxicity in Tumor Infiltrating Lymphocytes of Advanced Breast Cancer Patients by in vitro Stimulation with Tumor Antigen-Pulsed Autologous Dendritic Cells
Kass R, Bellone S, Palmieri M, Canè S, Bignotti E, Henry-Tillman R, Hutchins L, Cannon MJ, Klimberg S, Santin AD. Restoration of Tumor-Specific HLA Class I Restricted Cytotoxicity in Tumor Infiltrating Lymphocytes of Advanced Breast Cancer Patients by in vitro Stimulation with Tumor Antigen-Pulsed Autologous Dendritic Cells. Breast Cancer Research And Treatment 2003, 80: 275-285. PMID: 14503800, DOI: 10.1023/a:1024938215782.Peer-Reviewed Original ResearchConceptsPeripheral blood lymphocytesCytotoxic T lymphocytesTumor-specific cytotoxic T lymphocytesTumor-specific lytic activityAdvanced breast cancer patientsBreast cancer patientsCancer patientsInterleukin-2Breast cancerAnti-HLA class I mAbsNK-sensitive cell line K562Tumor-specific T-cell responsesChemotherapy-resistant breast cancerAdoptive T-cell immunotherapyAutologous dendritic cellsTh1 cytokine biasAutologous tumor cellsResistant breast cancerT cell responsesTumor-Infiltrating LymphocytesDendritic cell stimulationT cell populationsT-cell immunotherapyPotential of tumorHLA class I
2002
Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer
Cannon MJ, O’Brien T, Underwood LJ, Crew MD, Bondurant KL, Santin AD. Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer. Expert Review Of Anticancer Therapy 2002, 2: 97-105. PMID: 12113075, DOI: 10.1586/14737140.2.1.97.Peer-Reviewed Original ResearchConceptsDendritic cell-based immunotherapyCell-based immunotherapyPowerful antigen-presenting cellsPrimary T cell responsesDendritic cell vaccinationT cell responsesOvarian tumor antigenTumor-specific target antigensAntigen-presenting cellsTumor-specific antigensEffective immune responseCell vaccinationDendritic cellsMalignant diseaseOvarian cancerImmune responseTumor antigensTarget antigenImmunotherapyAntigenNovel targetVaccinationRecent recognitionCellsTumors
2000
Development and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Coke C, Pecorelli S, Cannon MJ, Parham GP. Development and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer. Gynecologic And Obstetric Investigation 2000, 49: 194-203. PMID: 10729762, DOI: 10.1159/000010246.Peer-Reviewed Original ResearchMeSH KeywordsAgedCD56 AntigenCD8-Positive T-LymphocytesCombined Modality TherapyDendritic CellsEndometrial NeoplasmsFemaleFlow CytometryHepatic ArteryHistocompatibility Antigens Class IHumansImmunophenotypingImmunotherapy, AdoptiveLiver NeoplasmsL-Lactate DehydrogenaseT-LymphocytesTomography, X-Ray ComputedUric AcidConceptsAutologous dendritic cellsDendritic cellsT cellsLiver metastasesEndometrial cancerAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingType 1 cytokine biasTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsLarge liver metastasesMetastatic endometrial cancerAutologous tumor cellsTumor-specific CD8T cell responsesEpstein-Barr virus-transformed lymphoblastoid cellsSerum uric acidIntracellular IFN-gammaBlood T cellsLactate dehydrogenaseT-cell immunotherapyLarge tumor massSerial time pointsDevelopment, 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 lymphocytesLymph node metastases
Santin A. Lymph node metastases. Cancer 2000, 88: 175-179. PMID: 10618621, DOI: 10.1002/(sici)1097-0142(20000101)88:1<175::aid-cncr24>3.0.co;2-f.Peer-Reviewed Original ResearchConceptsRegional lymph nodesSecondary lymphoid organsLymph nodesImmune systemCancer patientsLymphoid organsT cellsUninvolved regional lymph nodesTumor cellsTumor-bearing hostsNaive T cellsHost immune systemT cell activationNovel immunotherapeutic toolsActive immunotherapyImmunotherapy protocolsDendritic cellsHematogenous disseminationRLN dissectionSurgical removalImmunotherapeutic toolRadical dissectionClinical trialsAnatomic barriersTumor antigens
1999
Expression of Surface Antigens During the Differentiation of Human Dendritic Cells vs Macrophages from Blood Monocytes in vitro
Santin A, Hermonat P, Ravaggi M, Chiriva-Internat M, Cannon M, Hiserodt J, Pecorell S, Parham G. Expression of Surface Antigens During the Differentiation of Human Dendritic Cells vs Macrophages from Blood Monocytes in vitro. Immunobiology 1999, 200: 187-204. PMID: 10416127, DOI: 10.1016/s0171-2985(99)80069-2.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, CD1Antigens, SurfaceB7-1 AntigenB7-2 AntigenCD40 AntigensCD58 AntigensCell AdhesionCell DifferentiationCell DivisionCells, CulturedDendritic CellsGranulocyte-Macrophage Colony-Stimulating FactorHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansImmunoglobulinsImmunophenotypingIntercellular Adhesion Molecule-1Interleukin-4Leukocytes, MononuclearLipopolysaccharide ReceptorsMacrophagesMembrane GlycoproteinsMonocytesT-LymphocytesConceptsDendritic cellsICAM-1 expressionMHC class IIBlood monocytesCostimulation moleculesDay 3Day 10MHC antigensCD14 expressionICAM-1Day 5Majority of DCNaive T cell primingClass IIDifferentiation of DCsProfessional antigen presenting cellsT cell primingHuman dendritic cellsMHC class II moleculesAntigen presenting cellsGM-CSF/ILClass II moleculesMHC class IImportant surface moleculesEarly time points