Journal
GENE THERAPY
Volume 17, Issue 4, Pages 459-468Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.165
Keywords
gastrin-releasing peptide; immunotherapy; prostate carcinoma; neutralizing antibody
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Funding
- China National Natural Science Fund Committee [30500458, 30701023, 30672464, 30572272, 30872393, 30772570]
- Natural Science Foundation of Jiangsu Province [BK 2007170, BK2007169]
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Gastrin-releasing peptide (GRP), a bombesin-like peptide, is an autocrine or paracrine growth factor that can stimulate the growth of various cancer cells, making it an ideal target antigen to develop vaccines against cancer. In this study, we developed a novel DNA vaccine that encodes six tandem repeats of B-cell epitope GRP(18-27) (GRP6) flanked by HSP65 as carrier and four tandem repeats of mycobacterial HSP70(407-426) (M4) as helper T-cell epitopes for enhancement of immunogenicity. When intramuscularly immunized to mice, this anti-GRP DNA vaccine-induced GRP-specific antibody ( Ab) responses that were at least 10-fold higher in magnitude compared with HSP65-GRP6 protein vaccine. Both prophylactic and therapeutic antitumor immunities induced by vaccination significantly suppressed the growth of GRP-dependent prostate carcinoma RM-1 in vivo and prolonged the survival of tumor-inoculated mice. Out results also showed that the immune sera with high titer of GRP-specific Abs effectively inhibited the growth of tumor in mice and dose dependently inhibited proliferation of cultured RM-1 cells in vitro, suggesting that the GRP neutralizing Ab is responsible for the protective and therapeutic antitumor activity of vaccination. These findings may be of great importance in the further exploration of the applications of growth factors identified in human in cancer therapy. Gene Therapy (2010) 17, 459-468; doi: 10.1038/gt.2009.165; published online 4 February 2010
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