Improved efficacy of DNA vaccination against prostate carcinoma by boosting with recombinant protein vaccine and by introduction of a novel adjuvant epitope.
DNA vaccine represents an attractive approach for cancer treatment by inducing active immune-deprivation of gastrin-releasing peptide (GRP) from tumor cells, the growth of which is dependent on the stimulation of GRP. In this study, we developed a DNA vaccine using a plasmid vector to deliver the immunogen of six copies of the B cell epitope GRP(18-27) (GRP6). In order to increase the potency of this DNA vaccine, multiple strategies have been applied including DNA-prime protein-boost immunization and introduction of a foreign T-helper epitope into DNA vaccine. Mice vaccinated DNA vaccine boosting with HSP65-GRP6 protein induced high titer and relatively high avidity of anti-GRP antibodies as well as inhibition effect on the growth of murine prostate carcinoma, superior to the treatment using DNA alone or BCG priming HSP65-GRP6 protein boosting. Furthermore, the introduction of a novel foreign T-helper epitope into the GRP DNA vaccine showed a markedly stronger humoral immune response against GRP and tumor rejection even than the DNA-prime protein-boost strategy. No further stronger immunogenicity of this foreign T-helper epitope modified DNA vaccine was observed even using the strategy of modified DNA vaccine-priming and HSP65-GRP6 boosting method. The data presented demonstrate that improvement of potency of anti-GRP DNA vaccine with the above two feasible approaches should offer useful methods in the development of new DNA vaccine against growth factors for cancer immunotherapy.
Lu
Yong
Y
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
Ouyang
Kedong
K
Fang
Jing
J
Zhang
Huiyong
H
Wu
Guojun
G
Ma
Yanjun
Y
Zhang
Yu
Y
Hu
Xiangbing
X
Jin
Liang
L
Cao
Rongyue
R
Fan
Hao
H
Li
Taiming
T
Liu
Jingjing
J
D000276:Adjuvants, Immunologic; D000818:Animals; D000915:Antibody Affinity; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019886:Gastrin-Releasing Peptide / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D018834:Chaperonin 60; D024101:Mitochondrial Proteins
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D019886:Gastrin-Releasing Peptide; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C064112:gastrin releasing peptide (18-27), Phe(25)-; C060293:HSPD1 protein, human; D018834:Chaperonin 60; D024101:Mitochondrial Proteins