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
References
1. Carson WE, Giri JG, Lindemann MJ, Linett ML, Ahdieh M, Paxton R, Anderson D, Eisenmann J, Grabstein K, Caligiuri MA. (1994)
Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.
J. Exp. Med., 180 (4): 1395-403. [PMID:7523571]
2. EMA. 
EU/3/16/1681: orphan designation- humanised monoclonal antibody targeting interleukin-15 for the treatment of eosinophilic oesophagitis.
Accessed on 11/01/2018. Modified on 11/01/2018. ema.europa.eu, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2016/07/human_orphan_001773.jsp&mid=WC0b01ac058001d12b
3. Finch DK, Midha A, Buchanan CL, Cochrane D, Craggs RI, Cruwys S, Grahames C, Kolbeck R, Lowe DC, Maltby J et al.. (2011)
Identification of a potent anti-IL-15 antibody with opposing mechanisms of action in vitro and in vivo.
Br. J. Pharmacol., 162 (2): 480-90. [PMID:20942844]
4. Liu X, Kirk PB, Chang T, Charych DH. (2017)
Conjugates of an il-15 moiety and a polymer.
Patent number: US20170035898. Assignee: Nektar Therapeutics. Priority date: 03/04/2014. Publication date: 09/02/2017.
5. Quéméner A, Maillasson M, Arzel L, Sicard B, Vomiandry R, Mortier E, Dubreuil D, Jacques Y, Lebreton J, Mathé-Allainmat M. (2017)
Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization.
J. Med. Chem., 60 (14): 6249-6272. [PMID:28657314]
6. Vicari AP, Schoepfer AM, Meresse B, Goffin L, Léger O, Josserand S, Guégan N, Yousefi S, Straumann A, Cerf-Bensussan N et al.. (2017)
Discovery and characterization of a novel humanized anti-IL-15 antibody and its relevance for the treatment of refractory celiac disease and eosinophilic esophagitis.
MAbs, 9 (6): 927-944. [PMID:28581883]
7. Waldmann TA. (2006)
The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design.
Nat. Rev. Immunol., 6 (8): 595-601. [PMID:16868550]
8. Zhu X, Marcus WD, Xu W, Lee HI, Han K, Egan JO, Yovandich JL, Rhode PR, Wong HC. (2009)
Novel human interleukin-15 agonists.
J. Immunol., 183 (6): 3598-607. [PMID:19710453]