ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Novel human interleukin-15 agonists.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 152 citations in OpenAlex.
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Enhancing HIV-1-specific CAR-T cell functional activity by treatment with a novel cytokine-based scaffold with IL-15 superagonist and TGF-β-neutralizing activity.Journal of virology · 2026Article
- Immunotherapy in acute myeloid leukemia: The antibodies, TriKEs, and CARs on the arduous road to cure.Blood reviews · 2026Review
- FDA Approval Summary: Nogapendekin Alfa Inbakicept-pmln with BCG for BCG-Unresponsive Carcinoma In Situ.Clinical cancer research : an official journal of the American Association for Cancer Research · 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
- The clinical landscape of CAR NK cells.Experimental hematology & oncology · 2025Review
- Neoleukin-2/15-armored CAR-NK cells sustain superior therapeutic efficacy in solid tumors via c-Myc/NRF1 activation.Signal transduction and targeted therapy · 2025Article
- From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy.Immunotherapy · 2025Review
- Bispecific Antibodies in Glioblastoma: Mechanistic Advances, Delivery Innovations, and Translational Challenges in Overcoming Immune Escape.International journal of medical sciences · 2025Review
- Co-expression of IL-15/IL-15Ra complex enhances NKG2D-CAR T cell-mediated anti-pancreatic cancer immunity by activating the JAK/STAT5 signaling pathway.Frontiers in immunology · 2025Article
- Article
- Improved antitumor effectiveness of oncolytic HSV-1 viruses engineered with IL-15/IL-15Rα complex combined with oncolytic HSV-1-aPD1 targets colon cancer.Scientific reports · 2024Article
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Stimulating the Antitumor Immune Response Using Immunocytokines: A Preclinical and Clinical Overview.Pharmaceutics · 2024Review
- Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803Molecular therapy. Oncology · 2024Article
- Cancer immunity by tissue-resident type 1 innate lymphoid cells and killer innate-like T cells.Immunological reviews · 2024Review
- Article
- Tri-specific killer engager: unleashing multi-synergic power against cancer.Exploration of targeted anti-tumor therapy · 2024Review
- Therapeutic approaches to enhance natural killer cell cytotoxicity.Frontiers in immunology · 2024Review
47 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
IL-15 is an immunostimulatory cytokine trans-presented with the IL-15 receptor alpha-chain to the shared IL-2/IL-15Rbeta and common gamma-chains displayed on the surface of T cells and NK cells. To further define the functionally important regions of this cytokine, activity and binding studies were conducted on human IL-15 muteins generated by site-directed mutagenesis. Amino acid substitutions of the asparagine residue at position 72, which is located at the end of helix C, were found to provide both partial agonist and superagonist activity, with various nonconservative substitutions providing enhanced activity. Particularly, the N72D substitution provided a 4-5-fold increase in biological activity of the IL-15 mutein compared with the native molecule based on proliferation assays with cells bearing human IL-15Rbeta and common gamma-chains. The IL-15N72D mutein exhibited superagonist activity through improved binding ability to the human IL-15Rbeta-chain. However, the enhanced potency of IL-15N72D was not observed with cells expressing the mouse IL-15Ralpha-IL-15Rbeta-gamma(c) complex, suggesting that this effect is specific to the human IL-15 receptor. The enhanced biological activity of IL-15N72D was associated with more intense phosphorylation of Jak1 and Stat5 and better anti-apoptotic activity compared with the wild-type IL-15. IL-15N72D superagonist activity was also preserved when linked to a single-chain TCR domain to generate a tumor-specific fusion protein. Thus, the human IL-15 superagonist muteins and fusions may create opportunities to construct more efficacious immunotherapeutic agents with clinical utility.
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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.