ALT-803   

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
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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.