2019
First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors
Strauss J, Heery CR, Kim JW, Jochems C, Donahue RN, Montgomery AS, McMahon S, Lamping E, Marté J, Madan RA, Bilusic M, Silver MR, Bertotti E, Schlom J, Gulley JL. First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors. Clinical Cancer Research 2019, 25: 99-109. PMID: 30131389, PMCID: PMC6320276, DOI: 10.1158/1078-0432.ccr-18-1512.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCell Line, TumorDNA FragmentationDrug-Related Side Effects and Adverse ReactionsFemaleHumansImmunoglobulin GInfluenza, HumanInterleukin-12Killer Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMaximum Tolerated DoseMiddle AgedNatural Killer T-CellsNeoplasmsNeoplasms, Second PrimaryReceptors, Antigen, T-CellRecombinant Fusion ProteinsTransaminasesConceptsTreatment-related adverse eventsAscending dose cohortsNHS-IL12Solid tumorsT-cell receptor sequencing analysisHuman phase I trialMultiple ascending dose cohortsSingle ascending dose (SAD) cohortsTumor-infiltrating lymphocyte densityPeripheral blood mononuclear cellsPeripheral immune cell subsetsDurable stable diseaseImmune checkpoint inhibitorsObjective tumor responsePhase II doseT-cell receptor diversityAdvanced solid tumorsFlu-like symptomsMetastatic solid tumorsPhase I trialNatural killer cellsImmune cell subsetsBlood mononuclear cellsWarrants further studyEnhanced antitumor activity
2006
Transferable anticancer innate immunity in spontaneous regression/complete resistance mice
Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J, Simpson AJ, Old LJ, Cui Z. Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 7753-7758. PMID: 16682640, PMCID: PMC1458507, DOI: 10.1073/pnas.0602382103.Peer-Reviewed Original ResearchConceptsNatural killer cellsKiller cellsCancer cellsInnate immunitySR/CR miceWT recipient miceSubsets of leukocytesBone marrow cellsFormation of rosettesEffector cellsWT miceRecipient miceCR miceHigh dosesLow dosesPeritoneal macrophagesKilling activityMarrow cellsMiceRapid cytolysisCancer challengesLeukocytesMacrophagesDistant sitesNeutrophils