2023
Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeLenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma model
2016
Evolving Immunotherapy Approaches for Renal Cell Carcinoma
Curtis SA, Cohen JV, Kluger HM. Evolving Immunotherapy Approaches for Renal Cell Carcinoma. Current Oncology Reports 2016, 18: 57. PMID: 27475806, DOI: 10.1007/s11912-016-0542-9.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMetastatic renal cell carcinomaCell carcinomaImmune therapy approachesCheckpoint inhibitorsCytokine therapyCytotoxic chemotherapyOverall survivalImmunotherapy approachesVaccine therapyImmune therapyImmune systemTherapyCell therapyCarcinomaTherapy approachesHigh rateSurvivalMorbidityChemotherapyMortality
2015
Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
2014
Induction of Antigen-Specific Immunity with a Vaccine Targeting NY-ESO-1 to the Dendritic Cell Receptor DEC-205
Dhodapkar MV, Sznol M, Zhao B, Wang D, Carvajal RD, Keohan ML, Chuang E, Sanborn RE, Lutzky J, Powderly J, Kluger H, Tejwani S, Green J, Ramakrishna V, Crocker A, Vitale L, Yellin M, Davis T, Keler T. Induction of Antigen-Specific Immunity with a Vaccine Targeting NY-ESO-1 to the Dendritic Cell Receptor DEC-205. Science Translational Medicine 2014, 6: 232ra51. PMID: 24739759, PMCID: PMC6151129, DOI: 10.1126/scitranslmed.3008068.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, CDAntigens, NeoplasmCancer VaccinesCytokinesDendritic CellsDose-Response Relationship, ImmunologicEpitopesFemaleHumansImmunity, CellularImmunity, HumoralImmunoglobulin GInterferon-gammaLectins, C-TypeLymphocyte SubsetsMaleMembrane ProteinsMiddle AgedMinor Histocompatibility AntigensReceptors, Cell SurfaceT-LymphocytesVaccinationConceptsNY-ESO-1Immune checkpoint inhibitorsDendritic cellsToll-like receptorsTumor regressionNY-ESO-1-expressing tumorsTumor antigen NY-ESO-1Presence of DCsRobust antigen-specific immune responsesAntigen-specific immune responsesAntigen NY-ESO-1Combination immunotherapy strategiesStabilization of diseaseGrade 3 toxicityObjective tumor regressionImmune checkpoint blockadeT cell immunityAntigen-specific immunityPhase 1 trialTumor-associated antigensReceptor-specific monoclonal antibodyCheckpoint inhibitorsAdvanced malignanciesCheckpoint blockadeMedian duration
2012
Immunotherapy for metastatic melanoma
Zito CR, Kluger HM. Immunotherapy for metastatic melanoma. Journal Of Cellular Biochemistry 2012, 113: 725-734. PMID: 22006439, DOI: 10.1002/jcb.23402.Peer-Reviewed Original ResearchConceptsMetastatic melanomaPromising investigational approachesTreatment of melanomaImmunogenic tumorsAntitumor immunityCTLA-4Interleukin-2First cytokineInvestigational approachesProlonged responseMelanomaMonoclonal antibodiesImmunotherapyTreatmentIpilimumabPatientsCytokinesTumorsSmall subsetDiseaseImmunityAntibodies