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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2D Structure
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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
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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.