ALT-803   Click here for help

GtoPdb Ligand ID: 9615

Synonyms: IL-15 N72D:IL-15RαSu/Fc | IL-15SA | N-803
Immunopharmacology Ligand
Compound class: Antibody
Comment: ALT-803 (N-803) is an IL-15 superagonist developed to promote immune activation [1]. It is being investigated as an immuno-oncology agent [2,6,8-9], as immunotherapy post-allogeneic transplantation for hematological malignancies [7], 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 (nogapendekin alfa) and IL-15Rαsushi domain/Fc fusion protein (inbakicept) 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 [1].
Image re-produced from Altor BioScience Corporation's ALT-803 fact sheet (download the pdf here).

COVID-19: ALT-803 is being evaluated for safety and efficacy as an immunostimulatory agent in patients with COVID-19. This study is predicated upon the hypothesis that activating NK and T cells, via the IL-15 pathway, in patients with mild-to-moderate stage COVID-19, might reduce viral load and protect against disease progression.
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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.

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Bioactivity Comments
ALT-803 promotes immune activation with anti-tumour activity against relapsed hematological malignancies in humans [4]. It has been shown to synergistically enhance the ADCC activity of therapeutic antibodies and anti-tumour activities of checkpoint inhibitors (anti-PD-1, anti-PD-L1 and anti-CTLA4 antibodies) in preclinical studies [5].
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Interleukin-15 receptor Hs Agonist Agonist 10.8 pEC50 - 1
⤷ pEC50 10.8 (EC50 1.56x10-11 M) [1]
Description: Evaluated using an IL-15 dependent 32Dβ cell proliferation assay.
Interleukin-15 receptor Hs Agonist Agonist ~12.3 pIC50 - 10
⤷ pIC50 ~12.3 (IC50 ~5x10-13 M) [10]
Description: Binding of rhIL-15N72D to hIL-15R in vitro.