2017
Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy.
Bernatchez C, Haymaker C, Hurwitz M, Kluger H, Tetzlaff M, Jackson N, Gergel I, Tagliaferri M, Zalevsky J, Hoch U, Fanton C, Iacucci E, Aung S, Imperiale M, Liao E, Bentebibel S, Tannir N, Hwu P, Sznol M, Diab A. Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 2545-2545. DOI: 10.1200/jco.2017.35.15_suppl.2545.Peer-Reviewed Original ResearchNKTR-214PD-1 expressionT-cell clonalityTumor microenvironmentNK cellsCell clonalityIL-2 receptor pathwayDays post doseDrug-related AEsImmune-related AEAnti-PD1 therapyCapillary leak syndromePhase 1/2 trialMetastatic solid tumorsFavorable safety profileImmune checkpoint genesSignificant tumor regressionTumor tissue samplesGene expression analysisCytotoxic markersEffector CD8Leak syndromeCheckpoint therapyPrior immunotherapyRegulatory cells
2013
Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma
Scortegagna M, Ruller C, Feng Y, Lazova R, Kluger H, Li JL, De SK, Rickert R, Pellecchia M, Bosenberg M, Ronai ZA. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma. Oncogene 2013, 33: 4330-4339. PMID: 24037523, PMCID: PMC3955742, DOI: 10.1038/onc.2013.383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorForkhead Box Protein O3Forkhead Transcription FactorsGene Knockout TechniquesHumansIndazolesLung NeoplasmsLymphatic MetastasisMelanoma, ExperimentalMiceMice, KnockoutMutation, MissenseProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafPTEN PhosphohydrolasePyrimidinesPyruvate Dehydrogenase Acetyl-Transferring KinaseSignal TransductionSkin NeoplasmsTissue Array AnalysisConceptsPhosphoinositide-dependent kinase 1Protein kinase CAGC kinasesSerine/threonine protein kinasePDK1 expressionThreonine protein kinaseImportant cellular processesDirect genetic evidenceGene expression analysisActivity of AktCellular processesProtein kinaseGenetic evidenceExpression analysisPDK1 deletionKinase 1Kinase CElevated phosphorylationGenetic inactivationKinaseMelanoma invasionMelanoma developmentColony formationPharmacological inhibitionInhibits metastasis