2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysis
2020
Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer
Fong L, Hotson A, Powderly JD, Sznol M, Heist RS, Choueiri TK, George S, Hughes BGM, Hellmann MD, Shepard DR, Rini BI, Kummar S, Weise AM, Riese MJ, Markman B, Emens LA, Mahadevan D, Luke JJ, Laport G, Brody JD, Hernandez-Aya L, Bonomi P, Goldman JW, Berim L, Renouf DJ, Goodwin RA, Munneke B, Ho PY, Hsieh J, McCaffery I, Kwei L, Willingham SB, Miller RA. Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer. Cancer Discovery 2020, 10: 40-53. PMID: 31732494, PMCID: PMC6954326, DOI: 10.1158/2159-8290.cd-19-0980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellDrug Resistance, NeoplasmFemaleFollow-Up StudiesFuransHumansKidney NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisPyridinesPyrimidinesReceptor, Adenosine A2ASalvage TherapySurvival RateConceptsRenal cell cancerPretreatment tumor biopsiesClinical responseGene expression signaturesCell cancerTumor biopsiesPD-1/PD-L1 inhibitorsPD-1/PD-L1Refractory renal cell cancerPhase I clinical trialL1 combination therapyRecruitment of CD8Targetable immune checkpointsDurable clinical benefitPD-L1 inhibitorsT cell repertoireAdenosine 2A receptorAntitumor immunityReceptor blockadeImmune checkpointsPD-L1L1 antibodyClinical benefitCombination therapyImmune cells
2019
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors
Bentebibel SE, Hurwitz ME, Bernatchez C, Haymaker C, Hudgens CW, Kluger HM, Tetzlaff MT, Tagliaferri MA, Zalevsky J, Hoch U, Fanton C, Aung S, Hwu P, Curti BD, Tannir NM, Sznol M, Diab A. A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discovery 2019, 9: 711-721. PMID: 30988166, DOI: 10.1158/2159-8290.cd-18-1495.Peer-Reviewed Original ResearchConceptsNKTR-214Tumor biopsiesDurable disease stabilizationImmuno-oncology agentsMulticenter phase IPathway-targeted agentsTreatment tumor biopsiesPhase II doseActivation of CD8Metastatic solid tumorsNatural killer cellsOutpatient regimenCheckpoint inhibitorsDisease stabilizationRegulatory cellsEffector phenotypeKiller cellsTreatment algorithmImmune activationTumor shrinkagePharmacodynamic markersImmune cellsClinical activityIL2 receptorHuman studies
2016
Atezolizumab, an Anti–Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study
McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, Powderly JD, Infante JR, Fassò M, Wang YV, Zou W, Hegde PS, Fine GD, Powles T. Atezolizumab, an Anti–Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. Journal Of Clinical Oncology 2016, 34: 833-842. PMID: 26755520, DOI: 10.1200/jco.2015.63.7421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellDose-Response Relationship, DrugDose-Response Relationship, ImmunologicFemaleHumansImmunohistochemistryKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedT-LymphocytesConceptsMetastatic renal cell carcinomaRenal cell carcinomaClinical activityCell carcinomaImmune cellsAnti-programmed death ligand 1 antibodyImmune-mediated adverse eventsNon-clear cell histologySolid Tumors version 1.1Death ligand 1 antibodyTumor-infiltrating immune cellsEnd pointFuhrman grade 4Phase Ia studyManageable safety profileObjective response ratePrimary end pointSecondary end pointsPD-L1 expressionPD-L1 stainingProgression-free survivalResponse Evaluation CriteriaEffector T cellsAcute phase proteinsGrade 4
2011
Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy.
Flies DB, Sandler BJ, Sznol M, Chen L. Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. The Yale Journal Of Biology And Medicine 2011, 84: 409-21. PMID: 22180678, PMCID: PMC3238327.Peer-Reviewed Original ResearchConceptsB7-H1/PDTumor-associated antigensImmune responseCancer immunotherapyMolecular pathwaysCancer-specific immune responsesImmune-mediated destructionSpecific immune responseCancer immunotherapy researchAnti-cancer effectsCoinhibitory functionImmunotherapeutic modalitiesCoinhibitory moleculesClinical evidenceImmunotherapy researchMalignant diseaseNew immunotherapeuticsImmune cellsImmune functionStromal cellsCancerMonoclonal antibodiesCancer cellsImmunotherapyCurrent knowledge