ArticleCytokine2011
IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization.
Article in Cytokine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed.
- N-803, an IL-15 Superagonist Complex as Maintenance Therapy After Allogeneic Donor Stem Cell Transplant for Acute Myeloid Leukemia or Myelodysplastic Syndrome; A Phase 2 Trial.Transplantation and cellular therapy · 2024Trial
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Synergistic restoration of NK cell cytotoxicity against solid tumors via sLTA-mediated dual-action modulation.Molecular biology reports · 2026Article
- NK cell immunotherapy after analytic treatment interruption is associated with HIV viral control.Molecular therapy. Advances · 2026Article
- PEG-RLI: A Long-Acting IL-15 Agonist That Produces Massive Levels of CD8Pharmaceutics · 2026Article
- Armed Oncolytic Myxoma Virus Induces Systemic Antitumor Immunity Against Solid Tumors in Immunocompetent Mice.Research square · 2026Article
- Natural and Engineered Cytokines as Cancer Therapeutics.Annual review of cancer biology · 2026Article
- IL-12-releasing nanoparticles for effective immunotherapy of metastatic ovarian cancer.Nature materials · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- NKTR-255, a polymer-conjugated IL-15, synergizes with CAR-T cell therapy to activate endogenous anti-tumor immunity and improve tumor control.bioRxiv : the preprint server for biology · 2025Article
- TIME for Endometrial Cancer: Advancements and Challenges in Therapeutic Targets for the Endometrial Cancer Tumor Immune Microenvironment.Cancer immunology research · 2025Review
- How multispecific molecules are transforming pharmacotherapy.Nature reviews. Drug discovery · 2025Review
- Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models.Oncoimmunology · 2025Article
- NK cell immunotherapy administered at the time of HIV recrudescence is associated with viral control.bioRxiv : the preprint server for biology · 2025Article
- IL-15 Superagonist SHR-1501 Enhances Immune Responses in Lung Cancer by Modulating Tumor Microenvironment.The clinical respiratory journal · 2025Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Structure and function of therapeutic antibodies approved by the US FDA in 2024.Antibody therapeutics · 2025Review
- Optimized expression of human interleukin-15 inBiotechnology reports (Amsterdam, Netherlands) · 2025Article
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
- Interleukin-15Rα-Sushi-Fc Fusion Protein Co-Hitchhikes Interleukin-15 and Pheophorbide A for Cancer Photoimmunotherapy.Pharmaceutics · 2025Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
IL-15, a promising cytokine for treating cancer and viral diseases, is presented in trans by the IL-15 receptor (IL-15R) alpha-chain to the IL-15Rβγc complex displayed on the surface of T cells and natural killer (NK) cells. We previously reported that an asparagine to aspartic acid substitution at amino acid 72 (N72D) of IL-15 provides a 4-5-fold increase in biological activity compared to the native molecule. In this report, we describe Chinese hamster ovary (CHO) cell expression of a soluble complex (IL-15 N72D:IL-15RαSu/Fc) consisting of the IL-15 N72D superagonist and a dimeric IL-15Rα sushi domain-IgG1 Fc fusion protein. A simple but readily scalable affinity and ion exchange chromatography method was developed to highly purify the complex having both IL-15 binding sites fully occupied. The immunostimulatory effects of this complex were confirmed using cell proliferation assays. Treatment of mice with a single intravenous dose of IL-15N72D:IL-15RαSu/Fc resulted in a significant increase in CD8+ T cells and NK cells that was not observed following IL-15 treatment. Pharmacokinetic analysis indicated that the complex has a 25-h half-life in mice which is considerably longer than <40-min half-life of IL-15. Thus, the enhanced activity of the IL-15N72D:IL-15RαSu/Fc complex is likely the result of the increased binding activity of IL-15N72D to IL-15Rβγc, optimized cytokine trans-presentation by the IL-15RαSu domain, the dimeric nature of the cytokine domain and its increased in vivo half-life compared to IL-15. These findings indicate that this IL-15 superagonist complex could serve as a superior immunostimulatory therapeutic agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.