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