ArticleThe Journal of clinical investigation2021
NKTR-255 is a polymer-conjugated IL-15 with unique mechanisms of action on T and natural killer cells.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Engineering cytokines for cancer immunotherapy: a systematic review.Frontiers in immunology · 2023Pooled it
- The polymeric nanovectors landscape for cancer immunotherapies towards advanced therapy medicinal products (ATMPs).Acta pharmaceutica Sinica. B · 2026Review
- PEG-RLI: A Long-Acting IL-15 Agonist That Produces Massive Levels of CD8Pharmaceutics · 2026Article
- 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
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Stimulating the Antitumor Immune Response Using Immunocytokines: A Preclinical and Clinical Overview.Pharmaceutics · 2024Review
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recent and future perspectives on engineering interferons and other cytokines as therapeutics.Trends in biochemical sciences · 2023Review
- IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer.bioRxiv : the preprint server for biology · 2023Article
- Improving NK cell function in multiple myeloma with NKTR-255, a novel polymer-conjugated human IL-15.Blood advances · 2023Article
- The role of interleukin-15 in the development and treatment of hematological malignancies.Frontiers in immunology · 2023Review
- The application of Interleukin-2 family cytokines in tumor immunotherapy research.Frontiers in immunology · 2023Review
- Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.Trends in immunology · 2022Review
- Interleukin 15 in Cell-Based Cancer Immunotherapy.International journal of molecular sciences · 2022Review
- Insights into the anticancer mechanisms of interleukin-15 from engineered cytokine therapies.The Journal of clinical investigation · 2021Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NKTR-255 is a PEG conjugate of recombinant human IL-15 (rhIL-15) being examined as a potential cancer immunotherapeutic. Since IL-15 responses can be mediated by trans or cis presentation via IL-15Rα or soluble IL-15/IL-15Rα complexes, we investigated the role of IL-15Rα in driving NKTR-255 responses using defined naive and memory OVA-specific CD8+ T cells (OT-I) and NK cells in mice. NKTR-255 induced a 2.5- and 2.0-fold expansion of CD8+ T and NK cells, respectively, in WT mice. In adoptive transfer studies, proliferation of naive and memory WT OT-I T cells in response to NKTR-255 was not impaired in IL-15Rα-/- mice, suggesting trans presentation was not utilized by NKTR-255. Interestingly, naive IL-15Rα-/- OT-I cells had deficient responses to NKTR-255, while memory IL-15Rα-/- OT-I cell responses were partially impaired, suggesting that naive CD8+ T cells are more dependent on cis presentation of NKTR-255 than memory CD8+ T cells. In bone marrow chimera studies, IL-15Rα-/- and WT NK cells present in WT recipients had similar responses to NKTR-255, suggesting that cis presentation is not utilized by NK cells. NKTR-255 could form soluble complexes with IL-15Rα; binding to murine IL-15Rα generated superagonists that preferentially stimulated NK cells, showing that conversion to IL-15Rβ agonist biases the response toward NK cells. These findings highlight the ability of NKTR-255 to utilize IL-15Rα for cis presentation and act as an IL-15Rαβ agonist on CD8+ T cells.
Indexed as
Identifiers
What OpenQuestion holds
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.