2014
Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy
Sznol M. Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy. The Cancer Journal 2014, 20: 290-295. PMID: 25098290, DOI: 10.1097/ppo.0000000000000056.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 blockadePD-L1 blockadeT cell responsesTumor-specific T-cell responsesB7-H1/PDCell responsesOverall risk-benefit ratioAntitumor T-cell responsesTumor microenvironmentAnimal tumor model systemsAbundant preclinical dataAutoimmune-like toxicitiesSubset of patientsRecent clinical trialsRisk-benefit ratioT lymphocyte suppressionEarly clinical developmentActivated T lymphocytesTumor model systemsCombination anticancer therapyClinical responseDurable responsesDeath-1Metastatic melanomaPreclinical dataSurvival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2014, 32: 1020-1030. PMID: 24590637, PMCID: PMC4811023, DOI: 10.1200/jco.2013.53.0105.Peer-Reviewed Original ResearchConceptsLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1
2013
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer
Sznol M, Chen L. Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer. Clinical Cancer Research 2013, 19: 1021-1034. PMID: 23460533, PMCID: PMC3702373, DOI: 10.1158/1078-0432.ccr-12-2063.Peer-Reviewed Original ResearchConceptsB7-H1PD-1PD-1/PDAnti-PD-1 antibodyTumor microenvironmentAccurate predictive biomarkersEncouraging safety profileLigand B7-H1Antitumor immune responseB7-H1 expressionSubset of patientsImmune suppressive moleculesT cell functionInitial clinical studiesActivated T lymphocytesAdvanced human cancersRemarkable antitumor activityB7-DCClinical responseMetastatic diseaseDeath-1Immune suppressionSafety profileLung cancerPredictive biomarkers
2012
Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. New England Journal Of Medicine 2012, 366: 2443-2454. PMID: 22658127, PMCID: PMC3544539, DOI: 10.1056/nejmoa1200690.Peer-Reviewed Original ResearchConceptsAnti-PD-1 antibodyCell lung cancerRenal cell cancerObjective responseLung cancerAdverse eventsPD-L1Drug-related adverse eventsPD-1 ligand expressionCastration-resistant prostate cancerImmune-related causesPretreatment tumor specimensAdverse event profilePD-L1 expressionPD-1-PDCumulative response rateBMS-936558Immune correlatesL1 pathwayAdvanced melanomaComplete responseDeath-1PD-1Negative tumorsPositive tumors
2010
Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies
Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies. Seminars In Oncology 2010, 37: 508-516. PMID: 21074066, DOI: 10.1053/j.seminoncol.2010.09.008.Peer-Reviewed Original ResearchConceptsDurable objective responsesPotent cellular immunityAnti-CD137 antibodyCellular immune responsesLigand PD-L1Reasonable safety profileSevere liver toxicityTumor response criteriaTransplantable murine tumorsDose-dependent effectSurface of antigenImmunostimulatory mAbsAntitumor immunityObjective responseDeath-1PD-L1Tumor immunityCellular immunitySafety profileLiver toxicityClinical activityT lymphocytesImmune responseTumor antigensAgonist antibody