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
2007
Advances in dendritic cell-based therapeutic vaccines for cervical cancer
Bellone S, Pecorelli S, Cannon MJ, Santin AD. Advances in dendritic cell-based therapeutic vaccines for cervical cancer. Expert Review Of Anticancer Therapy 2007, 7: 1473-1486. PMID: 17944571, DOI: 10.1586/14737140.7.10.1473.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlphapapillomavirusAnimalsAntigen PresentationAntigens, ViralCancer VaccinesClinical Trials as TopicCombined Modality TherapyDendritic CellsDisease ProgressionDNA-Binding ProteinsFemaleHumansMaleMiceNeoplasmsOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsPeptide FragmentsRepressor ProteinsT-Lymphocyte SubsetsUterine Cervical NeoplasmsConceptsCervical cancerDendritic cellsMetastatic diseaseTherapeutic vaccinesDendritic cell-based therapeutic vaccineE7 oncoproteinsPowerful antigen-presenting cellsRecurrent/metastatic diseasePrimary T cell responsesAutologous dendritic cellsInvasive cervical cancerHuman papillomavirus infectionT cell responsesTherapeutic clinical trialsTumor-specific target antigensAntigen-presenting cellsImportant risk factorImportant health problemNovel therapeutic strategiesPapillomavirus infectionRadical surgeryCervical dysplasiaCancer deathRisk factorsClinical trials
2006
Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients
Ravaggi A, Romani C, Pasinetti B, Tassi RA, Bignotti E, Bandiera E, Odicino FE, Ragnoli M, Donzelli C, Falchetti M, Calza S, Santin AD, Pecorelli S. Correlation between serological immune response analyzed by a new ELISA for HPV-16/18 E7 oncoprotein and clinical characteristics of cervical cancer patients. Archives Of Virology 2006, 151: 1899-1916. PMID: 16732494, DOI: 10.1007/s00705-006-0787-y.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralAntibody SpecificityBiomarkersBiotinCancer VaccinesCarcinomaDisease ProgressionDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin GOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus VaccinesPrecancerous ConditionsRecombinant ProteinsSensitivity and SpecificityStreptavidinUterine Cervical NeoplasmsVaccinationConceptsCervical cancer patientsCancer patientsHealthy womenHuman papillomavirusE7 oncoproteinsPre-invasive neoplasiaAutologous dendritic cellsSerological immune responsesCervical cancer developmentCapture ELISA methodType of responseHPV 16/18Clinical characteristicsDendritic cellsAntibody levelsAntibody inductionCervical carcinomaSerological evaluationAntibody prevalenceImmune responseAdjunctive toolPatientsCancer developmentELISA methodPotential marker
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 reactionTherapeutic vaccines for cervical cancer: dendritic cell-based immunotherapy.
Santin AD, Bellone S, Roman JJ, Burnett A, Cannon MJ, Pecorelli S. Therapeutic vaccines for cervical cancer: dendritic cell-based immunotherapy. Current Pharmaceutical Design 2005, 11: 3485-500. PMID: 16248803, DOI: 10.2174/138161205774414565.Peer-Reviewed Original ResearchConceptsCervical cancer patientsT cell responsesDendritic cellsCervical cancerCancer patientsE7 oncoproteinsLate-stage cervical cancer patientsTumor-specific T-cell responsesImmune systemCell responsesPowerful antigen-presenting cellsDendritic cell-based immunotherapyPrimary T cell responsesCell-mediated immune responsesAutologous dendritic cellsTherapeutic HPV vaccinesTreatment-induced immunosuppressionPrimary radiation therapyHuman papillomavirus infectionAdvanced cervical cancerCell-based immunotherapyTumor-specific target antigensAntigen-presenting cellsImportant risk factorGold standard treatment
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 IInduction 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
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 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
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 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 lymphocytes
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