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Synonyms: interleukin-15
Compound class:
Endogenous peptide in human, mouse or rat
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
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| Immunopharmacology Comments |
| IL-15 is 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]. IL-15 provides a self-sustaining signal that activates NK cells and enhances their killing function. It is important in the gastrointestinal tract where it controls the homeostasis and activation of T, B, and NK cells and IL-15 produced by activated monocytes/macrophages is vital for the survival of CD8+ memory T cells (essential for maintenance of responses to invading pathogens) [7]. As an activator of NK cells, IL-15 has been identified 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]. GT Biopharma have a specialised biologic in their oncology pipeline, that contains a modified form of IL-15. GTB-3550 is a tri-specific NK cell engager (or TriKE™), that is a single-chain, recombinant fusion protein that comprises the scFv regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies conjugated to IL-15. One scFv recognizes the anti-CD16 marker on NK cells and the other recognizes the CD33 marker on the tumour cells. The IL-15 component initiates a self-sustaining signal that activates NK cells and enhances their ability to kill the selectively targeted tumour cells. GTB-3550 has progressed to clinical evaluation for high-risk CD33 positive hematologic cancers (e.g. Ph 1/2 NCT03214666). |
