2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
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
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
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
2003
In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells11Supported in part by grants from the Arkansas Breast Cancer Research Program, the Arkansas Special Population Network (A-SPAN), and the Camillo Golgi Foundation, Brescia, Italy (to A.S.).
Kass R, Agha J, Bellone S, Palmieri M, Canè S, Bignotti E, Henry-Tillman R, Hutchins L, Cannon MJ, Klimberg S, Santin AD. In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells11Supported in part by grants from the Arkansas Breast Cancer Research Program, the Arkansas Special Population Network (A-SPAN), and the Camillo Golgi Foundation, Brescia, Italy (to A.S.). Journal Of Surgical Research 2003, 112: 189-197. PMID: 12888337, DOI: 10.1016/s0022-4804(03)00147-1.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntigens, NeoplasmBreast NeoplasmsCD8-Positive T-LymphocytesDendritic CellsFemaleGenes, MHC Class IHumansMiddle AgedTumor Cells, CulturedConceptsAutologous tumor cellsAdvanced breast cancerHLA class IAntigen-pulsed dendritic cellsIntracellular cytokine expressionDendritic cellsBreast cancerFlow cytometric analysisTumor cellsCytokine expressionClass IT lymphocytesAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor antigen-pulsed dendritic cellsTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsPowerful antigen-presenting cellsTwo-color flow cytometric analysisCytometric analysisPeripheral blood mononuclear cellsSurface markersVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesColor flow cytometric analysisBreast Cancer Research Program
2002
Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10
Santin AD, Bellone S, Palmieri M, Bossini B, Dunn D, Roman JJ, Pecorelli S, Cannon M, Parham GP. Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10. International Journal Of Radiation Oncology • Biology • Physics 2002, 54: 1345-1355. PMID: 12459356, DOI: 10.1016/s0360-3016(02)03757-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntigens, CD19Blood TransfusionB-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesCD56 AntigenCD8-Positive T-LymphocytesCytokinesFemaleFlow CytometryHumansImmunophenotypingInterleukin-10Killer Cells, NaturalLymphocyte SubsetsMembrane GlycoproteinsMiddle AgedPerforinPore Forming Cytotoxic ProteinsRadiotherapyReceptors, IgGReceptors, Interleukin-2Time FactorsUterine Cervical NeoplasmsConceptsBlood transfusionT cellsUntransfused groupIL-10Transfused groupNK cellsUntransfused patientsCervical cancerIL-2Immune functionB cellsElevated serum IL-10NK-sensitive target KCD4/CD8 ratioImmunoregulatory cytokine IL-10Depression of NKIncrease of CD8Perforin-positive CD8Radiation-induced immunosuppressionPercentage of CD4Serum IL-10HLA-DR expressionNK cell cytotoxicityNumber of CD8Advanced cervical cancer
2001
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
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
Induction 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 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 points
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