Improved efficacy of DNA vaccination against prostate carcinoma by boosting with recombinant protein vaccine and by introduction of a novel adjuvant epitope.

Abstract

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.

• Authors: Yong Lu, Kedong Ouyang, Jing Fang, Huiyong Zhang, Guojun Wu, Yanjun Ma, Yu Zhang, Xiangbing Hu, Liang Jin, Rongyue Cao, Hao Fan, Taiming Li, Jingjing Liu
• Journal: Vaccine (Vaccine) Vol. 27 Issue 39 Pg. 5411-8 (Aug 27 2009) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 19616501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Cancer Vaccines
• Epitopes, B-Lymphocyte
• Epitopes, T-Lymphocyte
• Heat-Shock Proteins
• Peptide Fragments
• Recombinant Fusion Proteins
• Vaccines, DNA
• Vaccines, Synthetic
• heat-shock protein 65, human
• gastrin releasing peptide (18-27), Phe(25)-
• Gastrin-Releasing Peptide

Topics

• Adjuvants, Immunologic
• Animals
• Antibody Affinity
• Cancer Vaccines (administration & dosage, immunology)
• Carcinoma (drug therapy, immunology)
• Cell Line
• Epitopes, B-Lymphocyte (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Gastrin-Releasing Peptide (immunology)
• Heat-Shock Proteins (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental (drug therapy, immunology)
• Peptide Fragments (immunology)
• Prostatic Neoplasms (drug therapy, immunology)
• Recombinant Fusion Proteins (immunology)
• Vaccines, DNA (administration & dosage, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)