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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View interactive charts of activity data across species
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Summary of Clinical Use Click here for help
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 Click here for help
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 it 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 tumour models, and is predicted to synergistically enhance the efficacy of other cancer drugs against solid tumours and haematological malignancies.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04385849 Study of the Safety of Therapeutic Treatment With an Immunomodulatory Agent (N-803) in Adults With COVID-19 Phase 1 Interventional ImmunityBio, Inc.
NCT02989844 Relapse Prophylaxis With N-803 for AML and MDS Pts Following Allo HSCT Phase 2 Interventional Masonic Cancer Center, University of Minnesota
NCT04505501 Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection Phase 2 Interventional Thai Red Cross AIDS Research Centre
NCT04808908 Effect of N-803 on B Cell Follicles in Antiretroviral Treated HIV Disease Phase 1 Interventional University of Minnesota
NCT03022825 QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer Phase 2/Phase 3 Interventional ImmunityBio, Inc.
NCT03520686 QUILT 2.023: A Study of N-803 in Combination With Current Standard of Care vs Standard of Care as First-Line Treatment for Patients With Stage 3 or 4 NSCLC. Phase 3 Interventional ImmunityBio, Inc.