2023
A modified IL-18 drug in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma
Schoenfeld D, Djureinovic D, Zhang L, Mann J, Huck J, Jilaveanu L, Ring A, Kluger H. A modified IL-18 drug in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma. The Oncologist 2023, 28: s7-s7. PMCID: PMC10445567, DOI: 10.1093/oncolo/oyad216.010.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaImmune cell depletion studiesCell depletion studiesT cellsAnti-tumor activityPreclinical modelsRENCA modelTumor growthNK cellsIL-18IL-18BPCell carcinomaAnti-PD-1/CTLAAnti-PD-1 therapyIntra-tumoral T cellsModest anti-tumor activityAnti-tumor immune responseCytokine/chemokine levelsCytokine/chemokine profilingDepletion studiesEarly phase clinical trialsDecoy receptor proteinEnrichment of CD8PD-1 blockade
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