Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces prophylactic and therapeutic antitumor activity in vivo.
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.
Yong
Lu
L
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China.
Huiyong
Zhang
Z
Jing
Hou
H
Huaqian
Wang
W
Xiangbing
Hu
H
Yanjun
Ma
M
Xiaoyu
Ge
G
Li
Huang
H
Yanan
Yang
Y
Rongyue
Cao
C
Hao
Fan
F
Jingjing
Liu
L
Jie
Wu
W
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002277:Carcinoma / Q000276:immunology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019886:Gastrin-Releasing Peptide / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology
D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D019886:Gastrin-Releasing Peptide