ArticleThe Journal of biological chemistry2016
Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Stroma-specific IL-15 coordinates epithelial IL-15Rα to promote intestinal epithelial repair.Science China. Life sciences · 2026Article
- Interleukin 15-Presenting Nanovesicles with Doxorubicin-Loaded Ferritin Cores for Cancer Immunochemotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.BMC cancer · 2024Article
- Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice.BMC neuroscience · 2024Article
- T cell-responsive macroporous hydrogels for in situ T cell expansion and enhanced antitumor efficacy.Biomaterials · 2023Article
- Separation of GVL from GVHD -location, location, location.Frontiers in immunology · 2023Review
- Interleukin 15 in Cell-Based Cancer Immunotherapy.International journal of molecular sciences · 2022Review
- Natural killer T cell immunotherapy combined with IL-15-expressing oncolytic virotherapy and PD-1 blockade mediates pancreatic tumor regression.Journal for immunotherapy of cancer · 2022Article
- A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells.International journal of molecular sciences · 2021Article
- Protective and Therapeutic Effects of an IL-15:IL-15Rα-Secreting Cell-Based Cancer Vaccine Using a Baculovirus System.Cancers · 2021Article
- Heterodimeric IL-15 in Cancer Immunotherapy.Cancers · 2021Review
- Nanoparticle-Based Therapies for Turning Cold Tumors Hot: How to Treat an Immunosuppressive Tumor Microenvironment.Frontiers in bioengineering and biotechnology · 2021Review
- Protective Immune Responses Elicited by Deglycosylated Live-Attenuated Simian Immunodeficiency Virus Vaccine Are Associated with IL-15 Effector Functions.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- T cell immunotherapy enhanced by designer biomaterials.Biomaterials · 2019Review
- The molecular landscape of glioma in patients with Neurofibromatosis 1.Nature medicine · 2019Article
- The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival.Communications biology · 2019Article
- IL-15/IL-15Rα/CD80-expressing AML cell vaccines eradicate minimal residual disease in leukemic mice.Blood advances · 2018Article
- Nanoparticles: augmenting tumor antigen presentation for vaccine and immunotherapy treatments of cancer.Nanomedicine (London, England) · 2017Review
- Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer.Journal for immunotherapy of cancer · 2017Article
- The era of bioengineering: how will this affect the next generation of cancer immunotherapy?Journal of translational medicine · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Here we report a "configuration-dependent" mechanism of action for IL-15:IL-15Rα (heterodimeric IL-15 or hetIL-15) where the manner by which IL-15:IL-15Rα molecules are presented to target cells significantly affects its function as a vaccine adjuvant. Although the cellular mechanism of IL-15 trans-presentation via IL-15Rα and its importance for IL-15 function have been described, the full effect of the IL-15:IL-15Rα configuration on responding cells is not yet known. We found that trans-presenting IL-15:IL-15Rα in a multivalent fashion on the surface of antigen-encapsulating nanoparticles enhanced the ability of nanoparticle-treated dendritic cells (DCs) to stimulate antigen-specific CD8(+) T cell responses. Localization of multivalent IL-15:IL-15Rα and encapsulated antigen to the same DC led to maximal T cell responses. Strikingly, DCs incubated with IL-15:IL-15Rα-coated nanoparticles displayed higher levels of functional IL-15 on the cell surface, implicating a mechanism for nanoparticle-mediated transfer of IL-15 to the DC surface. Using artificial antigen-presenting cells to highlight the effect of IL-15 configuration on DCs, we showed that artificial antigen-presenting cells presenting IL-15:IL-15Rα increased the sensitivity and magnitude of the T cell response, whereas IL-2 enhanced the T cell response only when delivered in a paracrine fashion. Therefore, the mode of cytokine presentation (configuration) is important for optimal immune responses. We tested the effect of configuration dependence in an aggressive model of murine melanoma and demonstrated significantly delayed tumor progression induced by IL-15:IL-15Rα-coated nanoparticles in comparison with monovalent IL-15:IL-15Rα. The novel mechanism of IL-15 transfer to the surface of antigen-processing DCs may explain the enhanced potency of IL-15:IL-15Rα-coated nanoparticles for antigen delivery.
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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.