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Compound class: Peptide or derivative
Comment: ALT-803 is an IL-15 superagonist developed to promote immune activation. It is being investigated as an immuno-oncology agent, as immunotherapy post-allogeneic transplantation for hematological malignancies, and as an HIV therapy.
ALT-803 is produced from a high-yield recombinant mammalian cell line which co-expresses an IL-15 activation mutant, IL-15N72D and IL-15Rαsushi domain/Fc fusion protein as a stable soluble complex. The sushi domain increases transpresentation of the ALT-803 complex to the IL-2β/γ dimer which is the signal transducing component of the IL-15 receptor. The IgG Fc domain increases in vivo half-life.
Image re-produced from Altor BioScience Corporation's ALT-803 fact sheet (download the pdf here)
Ligand Activity Visualisation Charts
These 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.✖
|No information available.|
|Summary of Clinical Use|
|As of 25 July 2017, ClinicalTrials.gov had 28 registered trials involving ALT-803 (link to the list here), only one of which is Phase 2/3 (NCT03022825). ALT-803 is being evaluated across a range of solid and liquid tumours.|
|Mechanism Of Action and Pharmacodynamic Effects|
|IL-15 is a cytokine critical for the development, proliferation and activation of effector natural killer (NK) cells and CD8+ memory T cells, but its clinical utility is limited by its short in vivo half-life, and is technically difficult to produce. ALT-803 was developed as an IL-15 mimetic superagonist to overcome these problems. ALT-803 promotes robust and antigen-independent activity in various tumor models, and is predicted to synergistically enhance the efficacy of other cancer drugs against solid tumours and hematological malignancies.|