2008
Generation 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
2005
Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme
Bondurant KL, Crew MD, Santin AD, O'Brien TJ, Cannon MJ. Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme. Clinical Cancer Research 2005, 11: 3446-3454. PMID: 15867247, DOI: 10.1158/1078-0432.ccr-04-2043.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicDendritic CellsFemaleHLA-A2 AntigenHumansImmunodominant EpitopesInterferon-gammaInterleukin-4K562 CellsKallikreinsMolecular Sequence DataOvarian NeoplasmsPeptide FragmentsProtein BindingSerine EndopeptidasesT-Lymphocytes, CytotoxicConceptsSerine protease stratum corneum chymotryptic enzymeOvarian tumor cellsHelper T-cell epitopesAntigen-specific CD4T cell responsesDendritic cellsHLA-A2.1T cell epitopesCTL responsesCell epitopesTumor cellsCTL epitopesStratum corneum chymotryptic enzymeCell responsesPeptide-loaded dendritic cellsTumor antigen-specific CD8Helper T cell responsesT helper cell epitopesAntigen-specific CD8Attractive target antigenLevel of lysisDominant CD8Multiple CD8Chymotryptic enzymeHLA-DR
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 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
2003
Induction of tumor-specific cytotoxicity in tumor infiltrating lymphocytes by HPV16 and HPV18 E7-pulsed autologous dendritic cells in patients with cancer of the uterine cervix
Santin AD, Bellone S, Palmieri M, Bossini B, Roman JJ, Cannon MJ, Bignotti E, Canè S, Pecorelli S. Induction of tumor-specific cytotoxicity in tumor infiltrating lymphocytes by HPV16 and HPV18 E7-pulsed autologous dendritic cells in patients with cancer of the uterine cervix. Gynecologic Oncology 2003, 89: 271-280. PMID: 12713991, DOI: 10.1016/s0090-8258(03)00083-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultCytotoxicity, ImmunologicDendritic CellsDNA-Binding ProteinsFemaleFlow CytometryHumansImmunotherapy, AdoptiveInterferon-gammaInterleukin-4LeukocytesLymphocytes, Tumor-InfiltratingMembrane ProteinsOncogene Proteins, ViralPapillomavirus E7 ProteinsReceptors, Antigen, T-CellT-Lymphocytes, CytotoxicUterine Cervical NeoplasmsConceptsAutologous dendritic cellsAutologous tumor cellsCervical cancer patientsDendritic cellsPeripheral bloodT cellsTumor-specific cytotoxicityCancer patientsAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesAutologous tumor target cellsType 1 cytokine biasAnti-HLA class ICytotoxic T lymphocyte responsesIFN-gamma-positive cellsTwo-color flow cytometric analysisVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesTumor cellsAdoptive T-cell immunotherapyHPV18 E7 oncoproteinTumor-specific CTLsIntracellular cytokine expressionStandard treatment modalityT lymphocyte responsesT cell populations
2001
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
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 markersTumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix
Santin A, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G, Hermonat P. Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix. Gynecologic Oncology 2001, 81: 424-432. PMID: 11371133, DOI: 10.1006/gyno.2001.6200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedCarcinoma, Squamous CellCD4-CD8 RatioCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesFemaleHLA-DR AntigensHumansImmunophenotypingInterferon-gammaInterleukin-2Interleukin-4Lymph NodesLymphocytesLymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingReceptors, Interleukin-2Th1 CellsTh2 CellsUterine Cervical NeoplasmsConceptsType 1 cytokinesLymph nodesPeripheral bloodT cellsTumor tissueLymphocyte subsetsStage IB-IIA cervical cancerAntigen-experienced T lymphocytesIB-IIA cervical cancerTumor draining lymph nodeActivation markers HLA-DREarly activation markers CD25Draining Lymph NodesMarkers HLA-DRType 2 cytokinesCervical cancer patientsRegional lymph nodesActivation markers CD25Tumor-Infiltrating LymphocytesMajor leukocyte populationsFunction of lymphocytesCervical tumor tissuesDifferent anatomical sitesHLA-DRUterine cervixExpression 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 linesIntrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma.
Clemons-Miller AR, Chatta GS, Hutchins L, Angtuaco EJ, Ravaggi A, Santin AD, Cannon MJ. Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma. Clinical Cancer Research 2001, 7: 917s-924s. PMID: 11300492.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmB-LymphocytesCD8-Positive T-LymphocytesCytokinesDendritic CellsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGp100 Melanoma AntigenHumansImmunotherapyImmunotherapy, AdoptiveIndiumInterferon-gammaInterleukin-2Interleukin-4Interleukin-6MART-1 AntigenMelanomaMembrane GlycoproteinsMeningeal NeoplasmsMiddle AgedMonophenol MonooxygenaseNeoplasm ProteinsProteinsReverse Transcriptase Polymerase Chain ReactionTime FactorsTissue DistributionT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Necrosis Factor-alphaConceptsTumor necrosis factor alphaNecrosis factor alphaNeurological symptomsLeptomeningeal melanomaFactor alphaLow-dose IL-2 administrationType 1 cytokine profileAutologous dendritic cellsIL-2 administrationRight carotid arteryIntra-arterial deliveryT-cell immunotherapyGreater lytic activityLoss of hearingCTL infusionCytokine profileAutologous EBVDendritic cellsRecurrent melanomaOmmaya reservoirSpecific CTLIL-6IL-4Specific lysisLower extremities
2000
Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix
Santin A, Hermonat P, Ravaggi A, Bellone S, Roman J, Pecorelli S, Cannon M, Parham G. Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix. International Journal Of Radiation Oncology • Biology • Physics 2000, 48: 997-1006. PMID: 11072156, DOI: 10.1016/s0360-3016(00)00769-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsCisplatinCombined Modality TherapyFemaleHumansImmunity, CellularInterferon-gammaInterleukin-2Killer Cells, NaturalLymphocyte ActivationLymphocyte SubsetsMembrane GlycoproteinsMiddle AgedPerforinPore Forming Cytotoxic ProteinsProspective StudiesReceptors, Interleukin-2Uterine Cervical NeoplasmsConceptsT cellsIL-2Lymphoblast transformationRadiation therapyImmune functionNatural killer cytotoxic activityCD25-positive lymphocytesRadiation-induced immunosuppressionPercentage of CD8Advanced cervical cancerT cell numbersNatural killer cellsT cell subsetsActivation markers CD25C-RTMean absolute numberB cell numbersK562 cellsCisplatinum administrationConcurrent cisplatinumLymphocyte subsetsNK cellsConcurrent administrationKiller cellsUterine cervixIn 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 activity
1999
Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer
Santin A, Hermonat P, Ravaggi A, Chiriva-Internati M, Zhan D, Pecorelli S, Parham G, Cannon M. Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer. Journal Of Virology 1999, 73: 5402-5410. PMID: 10364287, PMCID: PMC112596, DOI: 10.1128/jvi.73.7.5402-5410.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DivisionDendritic CellsDNA-Binding ProteinsFemaleHistocompatibility TestingHLA-A AntigensHLA-B AntigensHLA-C AntigensHumansImmunophenotypingInterferon-gammaInterleukin-4Intracellular FluidK562 CellsOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsAutologous dendritic cellsAutologous tumor cellsDendritic cellsHuman papillomavirus type 16Cervical cancerLymphoblastoid cell linesPapillomavirus type 16HPV 16CTL populationsT cellsType 16Autologous Epstein-Barr virus-transformed lymphoblastoid cell linesAnti-HLA class II antibodiesAutologous tumor target cellsAnti-HLA class ICytotoxic T lymphocyte responsesTwo-color flow cytometric analysisVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesT cell proliferative responsesTumor cellsPotential tumor-specific targetClass II antibodiesIntracellular cytokine expressionT lymphocyte responses
1998
Effects of retinoic acid combined with interferon‐gamma on the expression of major‐histocompatibility‐complex molecules and intercellular adhesion molecule‐1 in human cervical cancer
Santin A, Hermonat P, Ravaggi A, Chiriva‐Internati M, Hiserodt J, Tian E, Carter C, Pecorelli S, Parham G. Effects of retinoic acid combined with interferon‐gamma on the expression of major‐histocompatibility‐complex molecules and intercellular adhesion molecule‐1 in human cervical cancer. International Journal Of Cancer 1998, 75: 254-258. PMID: 9462716, DOI: 10.1002/(sici)1097-0215(19980119)75:2<254::aid-ijc14>3.0.co;2-d.Peer-Reviewed Original ResearchConceptsMHC class IIIFN-gammaHuman cervical cancerCervical cancerHLA classTrans retinoic acidMHC classI mRNA expressionRetinoic acidSurface antigenTumor cellsIntercellular adhesion molecule-1Biologic response modifiersICAM-1 antigenAdhesion molecule-1ICAM-1 moleculesUntreated tumor cellsCell linesCervical cancer cellsICAM-1 surfaceCervical carcinoma cell linesAnti-proliferative effectsHuman cervical cancer cellsHuman cervical carcinoma cell lineResponse modifiers
1996
Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer
Santin A, Hiserodt J, DiSaia P, Pecorelli S, Granger G. Differential Effects of High-Dose Gamma Irradiation on the Production of Transforming Growth Factor-Beta in Fresh and Established Human Ovarian Cancer. Gynecologic Oncology 1996, 61: 403-408. PMID: 8641623, DOI: 10.1006/gyno.1996.0164.Peer-Reviewed Original ResearchConceptsOvarian carcinoma cell linesCarcinoma cell linesOvarian tumorsFresh tumorsCell linesHigh dosesImmunoinhibitory cytokinesTumor cellsFresh ovarian tumorsTGF-beta secretionTGF-beta productionCytokines TNF-alphaFresh tumor cellsWeak immunological responseFresh tumor samplesHuman ovarian cancerHuman ovarian carcinoma cell linesTNF-alphaOvarian cancerImmunological responseIFN-gammaCytokinesTumorsTumor samplesContinuous cell linesEffects of cytokines combined with high‐dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule‐1 in human ovarian cancers
Santin A, Rose G, Hiserodt J, Fruehauf J, Eck L, Garcia R, Schranz V, Disaia P, Pecorelli S, Granger G. Effects of cytokines combined with high‐dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule‐1 in human ovarian cancers. International Journal Of Cancer 1996, 65: 688-694. PMID: 8598323, DOI: 10.1002/(sici)1097-0215(19960301)65:5<688::aid-ijc21>3.0.co;2-2.Peer-Reviewed Original ResearchConceptsMHC class 1TNF-alphaAntigen expressionIFN-gammaFresh tumorsOvarian cell linesTumor cellsIntercellular adhesion molecule-1Cell linesICAM-1 antigen expressionHuman ovarian cancer cell linesOvarian cancer cell linesMajor histocompatibility complex moleculesICAM-1 antigenCytokines TNF-alphaClass 1Adhesion molecule-1Human ovarian cancerHuman ovarian tumorsEffects of cytokinesHuman ovarian cell linesRemoval of cytokinesICAM-1 surfaceHistocompatibility complex moleculesCancer cell lines