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An Interleukin‐15 Fusion Protein Enhances the Oncolytic Effects of Myxoma Virus in a Murine Melanoma Model
Author(s) -
MacNeill Amy L,
Tosic Vesna,
Doty Rosalinda A,
Liu Jia,
McFadden Grant,
Roy Edward J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1087.13
Subject(s) - myxoma virus , oncolytic virus , virus , biology , virology , fusion protein , immunology , recombinant dna , biochemistry , gene
Myxoma virus (MYXV) has potential as an oncolytic virus, but is not fully effective as a single‐agent therapy. We hypothesized that intratumoral (IT) expression of interleukin‐15 (IL‐15) by MYXV would recruit cytotoxic effector cells and improve treatment efficacy. To test this, MYXV expressing a fluorescent protein (MYXV‐Tred) and MYXV‐Tred encoding murine IL‐15 (MYXV‐IL15) were evaluated in a murine melanoma model. C57/BL6 mice that received weekly IT injections of virus lived significantly longer than controls. Unexpectedly, the median survival time of mice treated with MYXV‐IL15 was similar to MYXV‐Tred. In MYXV‐IL15‐treated tumors, virus titer, IL‐15 concentration, lymphocyte grade, and CD3 + cell counts were elevated at 4 days post‐inoculation (dpi), but decreased at 7 dpi. In subsequent experiments, recombinant MYXV was injected IT every 3 days. Additionally, to further enhance IL‐15 functions, MYXV‐Tred was modified to express IL‐15 fused with IL‐15 receptor alpha (MYXV‐RLI). The median survival time and number of IT Ly‐49 + cells were significantly increased in RAG mice bearing melanomas treated with MYXV‐RLI compared with MYXV‐IL15. These findings suggest that IT expression of an IL‐15/IL‐15Rα fusion protein enhances the oncolytic effects of MYXV.