Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help

Steel, Jason C., Ramlogan, Charmaine A., Yu, Ping, Sakai, Yoshio, Forni, Guido, Waldmann, Thomas A. and Morris, John C. (2010) Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help. Cancer Research, 70 3: 1072-1081. doi:10.1158/0008-5472.CAN-09-1301


Author Steel, Jason C.
Ramlogan, Charmaine A.
Yu, Ping
Sakai, Yoshio
Forni, Guido
Waldmann, Thomas A.
Morris, John C.
Title Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2010-02-01
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-09-1301
Open Access Status
Volume 70
Issue 3
Start page 1072
End page 1081
Total pages 10
Place of publication Philadelphia, PA United States
Publisher American Association for Cancer Research
Language eng
Abstract Interleukin-15 (IL-15) stimulates the diffrentiation and proliferation of T, B, and natural killer cells; enhances CD8+ cytolytic T-ceII activity; helps maintain CD44hiCD8+ memory T cells; and stimulates immunoglobulin synthesis by B cells. IL-15 is trans-presented to effector cells by its receptor, IL-15Rα, expressed on dendritic cells (DC) and monocytes. We examined the antitumor effect of adenoviral-mediated gene transfer of IL-15 and IL-15Rα to augment a DC vaccine directed against the NEU (ErbB2) oncoprotein. Transgenic BALB-neuT mice vaccinated in late-stage tumor development with a DC vaccine expressing a truncated NEU antigen, IL-I5, and its receptor (DCAd.Neu+Ad-mIL-15+Ad.mlL-15Rα) were protected from mammary carcinomas, with 70% of animals tumor-free at 30 weeks compared with none of the animals vaccinated with NEU alone (DC Ad.Neu). The combination of neu, IL-15, and IL-15Rα gene transfer leads to a significaintly greater anti-NEU antibody response compared with mice treated with DCAd.Neu or DCAd.Neu combined with either IL-15 (DCAd.Neu+Ad.mlL-15) or lL-15Rα (DC Ad.Neu+Ad.mlL-15Rα). The antitumor effect was antibody mediated and involved modulation of NEU expression and signaIing. Depletion of CD4 + cells did not abrogate the antitumor effect of the vaccine, nor did it inhibit the induction of anti-NEU aritibodies. Coexpression of IL-15 and IL-15Rα in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4+ T-helper function.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 17 Mar 2015, 16:05:50 EST by Jason Steel on behalf of Medicine - Greenslopes Private Hospital