2023
1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original Research
2021
389 Phase II of CD40 agonistic antibody sotigalimab (APX005M) in combination with nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy
Weiss S, Sznol M, Shaheen M, Berciano-Guerrero M, Felip E, Rodríguez-Abreu D, Arance A, Boni V, Linette G, Schuchter L, Gonzalez-Cao M, Iannotti N, Ganti A, Hauke R, Berrocal A, Filbert E, Kluger H. 389 Phase II of CD40 agonistic antibody sotigalimab (APX005M) in combination with nivolumab in subjects with metastatic melanoma with confirmed disease progression on anti-PD-1 therapy. Journal For ImmunoTherapy Of Cancer 2021, 9: a422-a422. DOI: 10.1136/jitc-2021-sitc2021.389.Peer-Reviewed Original ResearchAnti-PD-1 therapyMelanoma patientsMetastatic melanomaTumor PD-L1 expressionEffective anti-tumor immunityArm phase II trialCD40 agonist antibodyRefractory melanoma patientsRefractory metastatic melanomaAdvanced melanoma patientsPD-1 blockadePD-L1 expressionPhase II trialAnti-tumor immunitySubset of patientsOverall safety profileMajority of AEsOptimal therapeutic applicationReceptor binding profileInstitutional review boardClinical study teamNebraska Medical CenterOpen labelII trialTolerability profileKDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockade
2017
Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients.
Sanborn R, Pishvaian M, Kluger H, Callahan M, Weise A, Lutzky J, Yellin M, Rawls T, Vitale L, Halim A, Keler T, Davis T, Rizvi N. Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients. Journal Of Clinical Oncology 2017, 35: 3007-3007. DOI: 10.1200/jco.2017.35.15_suppl.3007.Peer-Reviewed Original ResearchCRC patientsCancer patientsAnti-PD1 antibody nivolumabPD-1 inhibitor monotherapyCD8 T cell infiltrationDrug-related SAEsSerum chemokine levelsTarget lesion diametersAcute kidney injuryPD-L1 expressionPhase 2 studyAdvanced cancer patientsAnti-tumor immunityPost-treatment biopsiesSubset of patientsT cell infiltrationMotor-sensory neuropathyPhase 1 trialOptimal dosing strategiesPhase 2 cohortMajority of tumorsPhase 2 portionObjective PRsTreatment biopsiesChemokine levelsDistinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases.
Dhodapkar K, Boddupalli C, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar M. Distinct dominant T-cell receptors with a tissue resident memory phenotype in individual melanoma metastases. Journal Of Clinical Oncology 2017, 35: 3-3. DOI: 10.1200/jco.2017.35.7_suppl.3.Peer-Reviewed Original ResearchInhibitory immune checkpointsTissue-resident memory TT cellsIndividual metastasesMelanoma metastasesDominant T-cell receptorReduced T cell infiltrationTissue-resident memory phenotypeEffective anti-tumor immunityT-cell receptor sequencingTumor cellsExome sequencingResident memory phenotypeResident memory TT RM cellsAnti-tumor immunityT cell infiltrationCell receptor sequencingT cell subsetsAntibody-mediated blockadeT-cell contentVascular endothelial growth factorSingle-cell mass cytometryCell mass cytometryEndothelial growth factor