2018
ATIM-39. IMPROVED SURVIVAL NOTED IN GLIOBLASTOMA PATIENTS TREATED WITH ADJUVANT TLR-3 AGONIST IN SETTING OF AUTOLOGOUS LYSATE-PULSED DC VACCINATION
Antonios J, Everson R, Soto H, Khattab S, Bethel J, Sun M, Mochizuki A, Lee A, Odesa S, Billingslea-Yoon E, Moughon D, Wang A, Cloughesy T, Prins R, Liau L. ATIM-39. IMPROVED SURVIVAL NOTED IN GLIOBLASTOMA PATIENTS TREATED WITH ADJUVANT TLR-3 AGONIST IN SETTING OF AUTOLOGOUS LYSATE-PULSED DC VACCINATION. Neuro-Oncology 2018, 20: vi10-vi10. PMCID: PMC6216157, DOI: 10.1093/neuonc/noy148.034.Peer-Reviewed Original ResearchToll-like receptorsMedian survivalDendritic cellsDC vaccinesGrade III or IV gliomaTumor lysate-pulsed DCGlioblastoma multiformePoly ICLCAutologous tumor lysateDC vaccine treatmentLysate-pulsed DCMGMT methylated tumorsMGMT unmethylated tumorsTLR-7 agonistPeripheral blood mononuclear cellsGrade III tumorsTLR-3 agonistIncreased overall survivalGrade IV tumorsBlood mononuclear cellsModulate immune responsesIII tumorsIV tumorsMethylated tumorsOverall survival
2017
Detection of immune responses after immunotherapy in glioblastoma using PET and MRI
Antonios J, Soto H, Everson R, Moughon D, Wang A, Orpilla J, Radu C, Ellingson B, Lee J, Cloughesy T, Phelps M, Czernin J, Liau L, Prins R. Detection of immune responses after immunotherapy in glioblastoma using PET and MRI. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 10220-10225. PMID: 28874539, PMCID: PMC5617282, DOI: 10.1073/pnas.1706689114.Peer-Reviewed Original ResearchConceptsPD-1Dendritic cellsMAb blockadeTumor lysate-pulsed DC vaccineHost antitumor immune responseTreated with dendritic cellsImmune responseDetection of immune responsesClinical management of patientsPET probeAntitumor immune responseTumor-infiltrating lymphocytesSyngeneic immunocompetent miceContrast enhancementSecondary lymphoid organsContrast-enhanced MRIManagement of patientsProbe uptakeNoninvasive imaging techniquesImmune inflammatory responseDC vaccinesImmunocompetent miceIntracranial tumorsImaging techniquesMalignant gliomasImmunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma
Antonios J, Soto H, Everson R, Moughon D, Orpilla J, Shin N, Sedighim S, Treger J, Odesa S, Tucker A, Yong W, Li G, Cloughesy T, Liau L, Prins R. Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma. Neuro-Oncology 2017, 19: 796-807. PMID: 28115578, PMCID: PMC5464463, DOI: 10.1093/neuonc/now287.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalB7-H1 AntigenCancer VaccinesFemaleGlioblastomaHumansLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLMyeloid CellsProgrammed Cell Death 1 ReceptorReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsTumor-infiltrating myeloid cellsAdaptive immune resistancePD-1 mAbCSF-1RiPD-1Immune resistancePD-L1Dendritic cellsMyeloid cellsColony stimulating factor 1 receptor inhibitorAnti-PD-1 monoclonal antibodyResponse to dendritic cellsIn vivo preclinical modelsPD-1 blockadePD-L1 expressionTumor-infiltrating lymphocytesPD-1/PD-L1Measured overall survivalSignificant survival benefitDevelopment of immune resistanceCytolysis in vitroLong-term survivalDC vaccinesTIL infiltrationOverall survivalChapter 12 Dendritic Cell Therapy for Brain Tumors
Everson R, Antonios J, Tucker A, Liau L. Chapter 12 Dendritic Cell Therapy for Brain Tumors. 2017, 301-321. DOI: 10.1016/b978-0-12-802420-1.00012-0.Peer-Reviewed Original ResearchDC therapyDendritic cellsClinical trialsEvidence of immune responsesImmune responseLimitations of current treatment optionsTreatment of malignant gliomasDendritic cell therapyAntitumor immune responseAntigen presenting abilityCurrent treatment optionsDevelopment of alternative modalitiesDC vaccinesActive immunotherapyProlonged survivalMalignant gliomasPreclinical modelsTreatment optionsTumor cellsCell therapyClinical effectsVaccine formulationsBrain tumorsImmune systemBrain parenchyma
2016
IMST-28. NON-INVASIVE IMMUNE MONITORING FOLLOWING DC VACCINATION EFFECTIVELY DELINEATES IMMUNE RESPONSES IN GLIOBLASTOMA
Antonios J, Soto H, Everson R, Orpilla J, Shin N, Nathanson D, Harris R, Sadeghi S, Ellingson B, Liau L, Prins R. IMST-28. NON-INVASIVE IMMUNE MONITORING FOLLOWING DC VACCINATION EFFECTIVELY DELINEATES IMMUNE RESPONSES IN GLIOBLASTOMA. Neuro-Oncology 2016, 18: vi92-vi92. DOI: 10.1093/neuonc/now212.384.Peer-Reviewed Original ResearchDC vaccinesImmune monitoringFACS analysisPD-1Immune monitoring of patientsActivated tumor-infiltrating lymphocytesDC vaccine treatmentTumor-infiltrating lymphocytesImmunocompetent C57BL/6 miceMAb-treated miceTumor-bearing hemisphereGL261 glioma cellsPET signal intensityActive lymphocytic infiltrationImmunotherapy fieldMonitoring of patientsMedian survivalStandard chemotherapyClinically relevant modalityMeasures of immune responseNeedle biopsyLymphocytic infiltrationTreated miceLymphocyte responsesNon-invasiveIMST-56. TUMOR LYSATE-PULSED DC VACCINATION INDUCES NEOANTIGEN-SPECIFIC T CELL RESPONSES
Everson R, Shin N, Antonios J, Soto H, Tucker A, Zaretsky J, Orpilla J, Rathe S, Popescu F, Largaespada D, Liau L, Prins R. IMST-56. TUMOR LYSATE-PULSED DC VACCINATION INDUCES NEOANTIGEN-SPECIFIC T CELL RESPONSES. Neuro-Oncology 2016, 18: vi99-vi99. DOI: 10.1093/neuonc/now212.412.Peer-Reviewed Original ResearchAutologous tumor lysateTumor-infiltrating lymphocytesTumor-specific mutationsDC vaccinesDendritic cellsCD8+ T cell responsesEnhanced T cell infiltrationTumor-infiltrating lymphocyte culturesImmune responseIntracranial GL261 gliomasT cell infiltrationT cell responsesPhase III trialsTreatment groupsRelevant target antigensMurine glioma cell lineDC therapyTCR clonotypesTumor lysateGL261 gliomasIII trialsNeoantigen peptidesOriginal tumorGlioma cell linesLymphocytic infiltrationPD-1 blockade enhances the vaccination-induced immune response in glioma
Antonios J, Soto H, Everson R, Orpilla J, Moughon D, Shin N, Sedighim S, Yong W, Li G, Cloughesy T, Liau L, Prins R. PD-1 blockade enhances the vaccination-induced immune response in glioma. JCI Insight 2016, 1: e87059. PMID: 27453950, PMCID: PMC4951098, DOI: 10.1172/jci.insight.87059.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesPD-1 blockadeDC vaccinesPD-1/PD-L1PD-1Survival benefitMAb blockadeProgrammed death-1/programmed death-ligand 1Effect of PD-1 blockadeBlockade of PD-1Induced T cell infiltrationIsolated tumor-infiltrating lymphocytesPD-1 pathway inhibitionActive vaccinationCD8<sup>+</sup> T cellsPD-1/PD-L1 pathwayImmune responseVaccination-induced immune responsesAutologous tumor lysateIntratumoral immune responseNegative costimulatory pathwaysAdaptive immune resistanceDeath-ligand 1T cell infiltrationTumor cell cytolysisTCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination
Hsu M, Sedighim S, Wang T, Antonios J, Everson R, Tucker A, Du L, Emerson R, Yusko E, Sanders C, Robins H, Yong W, Davidson T, Li G, Liau L, Prins R. TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination. Cancer Immunology Research 2016, 4: 412-418. PMID: 26968205, PMCID: PMC4873445, DOI: 10.1158/2326-6066.cir-15-0240.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesT cell receptorT-cell receptor sequencingImmune responseOverall survivalPeripheral bloodIncreased time to progressionTumour-infiltrating lymphocytes contentAssessment of tumor-infiltrating lymphocytesPredictors of immune responseAntigen-specific immune responsesTime to progressionDendritic cell immunotherapyDC vaccinesCell immunotherapyImmunotherapeutic strategiesSurvival outcomesStatistically significant correlationT cellsClinical outcomesAdjunctive treatmentBrain tumorsImmunotherapyNext-generation sequencing approachTumor
2015
Dendritic cell immunotherapy for brain tumors
Antonios J, Everson R, Liau L. Dendritic cell immunotherapy for brain tumors. Journal Of Neuro-Oncology 2015, 123: 425-432. PMID: 26037466, DOI: 10.1007/s11060-015-1830-1.Peer-Reviewed Original ResearchConceptsDendritic cellsPatient-derived dendritic cellsDestruction of malignant cellsDendritic cell immunotherapyGlioma treatmentPre-clinical modelsCell immunotherapyDC vaccinesTreatment of gliomaActive immunotherapyProlonged survivalMalignant cellsImmunological targetsPatient-specific treatmentClinical trialsImmune responseTherapeutic approachesBrain tumorsBrain parenchymaGliomaImmunotherapyTreatmentBrainCellsImmunosuppression