A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases

Abstract

AbstractBackgroundThe cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has spurred interest in using IL-2 for immunotherapy of cancer and autoimmune diseases. Thus, numerous IL-2-based biologic agents with improved bias or delivery toward effector immune cells or Treg cells have been developed. These improved IL-2-based compounds recently entered clinical trials.ObjectiveThis study systematically reviews clinical results of improved IL-2-based compounds for the treatment of cancer or autoimmune diseases.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), searched theClinicalTrials.govdatabase for registered IL-2 trials using improved IL-2-based agents and different databases for available results of these studies.ResultsWe identified 547 registered clinical trials, of which we extracted 36 studies on improved IL-2-based compounds. Moreover, we assessed another 9 agents reported in two recent literature reviews and based on our knowledge, totaling in 45 improved IL-2-based compounds. A secondary search for registered clinical trials of each of these improved 45 compounds resulted in 139 clinical trials included in this systematic review, with 29 trials reporting clinical results.ConclusionsAs of yet, none of the improved IL-2-based compounds gained regulatory approval for the treatment of cancer or autoimmune diseases. Three compounds treating cancer have entered phase 3 trials with two studies still ongoing. NKTR-214 is the only compound that has completed phase 3 studies. The PIVOT IO-001 study testing the combination of NKTR-214 plus Pembrolizumab compared to Pembrolizumab monotherapy in metastatic melanoma missed its primary endpoint of superior objective response rate and progression-free survival. The PIVOT-09 study, combining NKTR-214 with Nivolumab compared to Sunitinib or Cabozantinib in advanced renal cell carcinoma, missed its primary endpoint of improved objective response rate. Trials in autoimmune diseases are currently in early stages, thus not allowing conclusions on efficacy. Results of ongoing trials will provide insight into which improved IL-2-based compounds will be beneficial for cancer and autoimmune diseases.