GtoPdb Ligand ID: 9615

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)
2D Structure
Click here for structure editor
No information available.
Summary of Clinical Use
As of 25 July 2017, 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.