Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer

Morris, J. C., Ramlogan-Steel, C. A., Yu, P., Black, B. A., Mannan, P., Allison, J. P., Waldmann, T. A. and Steel, J. C. (2014) Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer. Gene Therapy, 21 4: 393-401. doi:10.1038/gt.2014.10


Author Morris, J. C.
Ramlogan-Steel, C. A.
Yu, P.
Black, B. A.
Mannan, P.
Allison, J. P.
Waldmann, T. A.
Steel, J. C.
Title Vaccination with tumor cells expressing IL-15 and IL-15Rα inhibits murine breast and prostate cancer
Journal name Gene Therapy   Check publisher's open access policy
ISSN 1476-5462
0969-7128
Publication date 2014-04-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/gt.2014.10
Volume 21
Issue 4
Start page 393
End page 401
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted abstract
A number of antitumor vaccines have recently shown promise in upregulating immune responses against tumor antigens and improving patient survival. In this study, we examine the effectiveness of vaccination using interleukin (IL)-15-expressing tumor cells and also examine their ability to upregulate immune responses to tumor antigens. We demonstrated that the coexpression of IL-15 with its receptor, IL-15Rα, increased the cell-surface expression and secretion of IL-15. We show that a gene transfer approach using recombinant adenovirus to express IL-15 and IL-15Rα in murine TRAMP-C2 prostate or TS/A breast tumors induced antitumor immune responses. From this, we developed a vaccine platform, consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells coexpressing IL-15 and IL-15Rα that inhibited tumor formation when mice were challenged with tumor. Inhibition of tumor growth led to improved survival when compared with animals receiving cells expressing IL-15 alone or unmodified tumor cells. Animals vaccinated with tumor cells coexpressing IL-15 and IL-15Rα showed greater tumor infiltration with CD8+ T and natural killer (NK) cells, as well as increased antitumor CD8+ T-cell responses. Vaccination with IL-15/IL-15Rα-modified TS/A breast cancer cells provided a survival advantage to mice challenged with unrelated murine TUBO breast cancer cells, indicating the potential for allogeneic IL-15/IL-15Rα-expressing vaccines.
Keyword Tumor cells
Vaccinations
Breast cancer
Prostate cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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