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

journal contribution
posted on 08.08.2019, 00:00 by JC Morris, Charmaine Ramlogan-SteelCharmaine Ramlogan-Steel, P Yu, BA Black, P Mannan, JP Allison, TA Waldmann, Jason SteelJason Steel
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-15R, 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-15R 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-15R 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-15R 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-15R-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-15R-expressing vaccines. © 2014 Macmillan Publishers Limited.

Funding

Other

History

Volume

21

Issue

4

Start Page

393

End Page

401

Number of Pages

9

eISSN

1476-5462

ISSN

0969-7128

Publisher

Nature Publishing Group, UK

Peer Reviewed

Yes

Open Access

No

Acceptance Date

06/01/2014

External Author Affiliations

The University of Queensland; University of Cincinnati, National Cancer Institute, The University of Texas MD Anderson Cancer Center, USA

Era Eligible

Yes

Journal

Gene Therapy