Evidence map›Paper›PMID 25329832›Full record

ArticlePloS one2014

Myxoma virus expressing a fusion protein of interleukin-15 (IL15) and IL15 receptor alpha has enhanced antitumor activity.

Vesna Tosic, Diana L Thomas, David M Kranz, Jia Liu, Grant McFadden, Joanna L Shisler, Amy L MacNeill, Edward J Roy

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. OncolyticTurkish journal of haematology : official journal of Turkish Society of Haematology · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Therapeutic potential of interleukin-15 in cancer (Review).Experimental and therapeutic medicine · 2021
    Review
  14. Review
  15. Article
  16. Methods for the Construction of Recombinant Oncolytic Myxoma Viruses.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  17. Article
  18. Synergistic Combination of Oncolytic Virotherapy and Immunotherapy for Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  19. Oncolytic Virotherapy with Myxoma Virus.Journal of clinical medicine · 2020
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Vesna TosicDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Diana L ThomasNeuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
David M KranzDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Jia LiuDepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America.
Grant McFaddenDepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America.
Joanna L ShislerDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Amy L MacNeillDepartment of Pathobiology at College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Edward J RoyDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
University of Illinois Urbana-Champaign · USUniversity of Florida · US

Funding

Manipulation of inflammasomes and NF-kB signaling in human myeloid cells by MyxomR01AI100987 · NIAID · UNIVERSITY OF FLORIDA · PI MCFADDEN, GRANT · 2013 to 2017
$1.9M
Characterization of Antiviral Functions of Sterile Alpha Motif-Containing DomainK22AI099184 · NIAID · UNIV OF ARKANSAS FOR MED SCIS · PI LIU, JIA · 2013 to 2014
$268k
NIAID NIH HHS K22 AI099184NIAID NIH HHS R01 AI100987
6 · The paper itself

Abstract

Myxoma virus, a rabbit poxvirus, can efficiently infect various types of mouse and human cancer cells. It is a strict rabbit-specific pathogen, and is thought to be safe as a therapeutic agent in all non-rabbit hosts tested including mice and humans. Interleukin-15 (IL15) is an immuno-modulatory cytokine with significant potential for stimulating anti-tumor T lymphocytes and NK cells. Co-expression of IL15 with the α subunit of IL15 receptor (IL15Rα) greatly enhances IL15 stability and bioavailability. Therefore, we engineered a new recombinant myxoma virus (vMyx-IL15Rα-tdTr), which expresses an IL15Rα-IL15 fusion protein plus tdTomato red fluorescent reporter protein. Permissive rabbit kidney epithelial (RK-13) cells infected with vMyx-IL15Rα-tdTr expressed and secreted the IL15Rα-IL15 fusion protein. Functional activity was confirmed by demonstrating that the secreted fusion protein stimulated proliferation of cytokine-dependent CTLL-2 cells. Multi-step growth curves showed that murine melanoma (B16-F10 and B16.SIY) cell lines were permissive to vMyx-IL15Rα-tdTr infection. In vivo experiments in RAG1-/- mice showed that subcutaneous B16-F10 tumors treated with vMyx-IL15Rα-tdTr exhibited attenuated tumor growth and a significant survival benefit for the treated group compared to the PBS control and the control viruses (vMyx-IL15-tdTr and vMyx-tdTr). Immunohistological analysis of the subcutaneous tumors showed dramatically increased infiltration of NK cells in vMyx-IL15Rα-tdTr treated tumors compared to the controls. In vivo experiments with immunocompetent C57BL/6 mice revealed a strong infiltrate of both NK cells and CD8+ T cells in response to vMyx-IL15Rα-tdTr, and prolonged survival. We conclude that delivery of IL15Rα-IL15 in a myxoma virus vector stimulates both innate and adaptive components of the immune system.

Indexed as

AnimalsCell CountCell LineCell Line, TumorCell ProliferationDNA, RecombinantGenetic EngineeringInterleukin-15Interleukin-15 Receptor alpha SubunitKiller Cells, NaturalMelanomaMiceMyxoma virusOncolytic VirusesRecombinant Fusion ProteinsT-LymphocytesDNA, RecombinantInterleukin-15Interleukin-15 Receptor alpha SubunitRecombinant Fusion Proteins

Identifiers

PMID25329832
PMCPMC4199602
OpenAlexW2062368814

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.