ArticleGene therapy2015
Intramuscular delivery of heterodimeric IL-15 DNA in macaques produces systemic levels of bioactive cytokine inducing proliferation of NK and T cells.
Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- First-in-human phase I/Ib study of NIZ985, a recombinant heterodimer of IL-15 and IL-15Rα, as a single agent and in combination with spartalizumab in patients with advanced and metastatic solid tumors.Journal for immunotherapy of cancer · 2023Article
- Advancements in the development of nucleic acid vaccines for syphilis prevention and control.Human vaccines & immunotherapeutics · 2023Review
- Review
- Advances in the polymeric delivery of nucleic acid vaccines.Theranostics · 2022Review
- Phase I study of single agent NIZ985, a recombinant heterodimeric IL-15 agonist, in adult patients with metastatic or unresectable solid tumors.Journal for immunotherapy of cancer · 2021Article
- Heterodimeric IL-15 in Cancer Immunotherapy.Cancers · 2021Review
- Bench-to-bedside translation of interleukin-15 for immunotherapy: principles and challenges.Expert opinion on drug delivery · 2020Article
- Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10.Journal for immunotherapy of cancer · 2020Article
- Engineering DNA vaccines against infectious diseases.Acta biomaterialia · 2018Review
- Optimized administration of hetIL-15 expands lymphocytes and minimizes toxicity in rhesus macaques.Cytokine · 2018Article
- ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment.Journal of virology · 2018Article
- NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies.Frontiers in immunology · 2018Review
- Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes.Journal of extracellular vesicles · 2018Article
- Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity.Human vaccines & immunotherapeutics · 2017Review
- 1st International Conference on Human &Translational Immunology.Nature immunology · 2016Article
- Recombinant human heterodimeric IL-15 complex displays extensive and reproducible N- and O-linked glycosylation.Glycoconjugate journal · 2016Article
- Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity.The Journal of biological chemistry · 2016Article
- NK Cells in HIV Disease.Current HIV/AIDS reports · 2016Review
- Molecular mechanisms for enhanced DNA vaccine immunogenicity.Expert review of vaccines · 2016Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Interleukin-15 (IL-15) is a common γ-chain cytokine that has a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting infection and cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha (IL-15Rα) chain, which together form the IL-15 heterodimer. We have generated DNA vectors expressing the heterodimeric IL-15 by optimizing mRNA expression and protein trafficking. Repeated administration of these DNA plasmids by intramuscular injection followed by in vivo electroporation in rhesus macaques resulted in sustained high levels of IL-15 in plasma, with no significant toxicity. Administration of DNAs expressing heterodimeric IL-15 also resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8(+)NK cells, all memory CD8(+) T-cell subsets and effector memory CD4(+) T cells. Expression of heterodimeric IL-15 by DNA delivery to the muscle is an efficient procedure to obtain high systemic levels of bioactive cytokine, without the toxicity linked to the high transient cytokine peak associated with protein injection.
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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.