IL-15   

GtoPdb Ligand ID: 4981

Synonyms: interleukin-15
Comment: IL-15 and IL-2 are cytokines that share common biological effects, but also exhibit distinct, and sometimes competing, functions [7].
Nektar Therapeutics is developing a long-acting polymer-engineered (e.g. PEGylated) IL-15 conjugate, code named NKTR-255 (structure not disclosed), as a potential immuno-oncology agent- see their patent US20170035898 [4]. The conjugate has been optimised for binding to the IL-15Rα subunit and improved plasma and tumour exposure compared to native IL-15. This agent is in preclinical evaluation (August 2017).
Calypso Biotech have an anti-IL-15 monoclonal antibody named CALY-002 in their development pipeline. CALY-002 has potential for the treatment of refractory celiac disease and other inflammatory conditions at mucosal interfaces within the gastro-intestinal tract (e.g. eosinophilic esophagitis) [6]. The EMA granted CALY-002 orphan drug designation for the treatment of eosinophilic esophagitis in 2016 [2].
Species: Human
Immunopharmacology Comments
IL-15 is a cytokine mainly expressed by monocytes, dendritic cells and epithelial cells. It interacts with components of the IL-2 receptor despite having no sequence homology with IL-2 [1], and is markedly important in the gastrointestinal tract where it controls the homeostasis and activation of T, B, and NK cells. IL-15 produced by activated monocytes/macrophages is involved in regulation of human NK cells and is particularly vital for the survival of CD8+ memory T cells (essential for maintenance of responses to invading pathogens) [7]. IL-15 has been identied as a promising candidate for use as an immuno-oncology therapeutic, and engineered long-acting IL-15 conjugates are in development. Anti-IL-15 mAbs are in development for anti-inflammatory potential [3,6].