HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lu, Y. Articles by Jingjing, L. PubMed PubMed Citation Articles by Lu, Y. Articles by Jingjing, L.

Y Lu, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
D Mekoo, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
O Kedong, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
X Hu, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
Y Liu, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
M Lin, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
L Jin, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
R Cao, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
T Li, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
Z Yankai, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China
H Fan, Shanghai Yijiu Biomedical Cooperation Ltd, Shanghai, China
L Jingjing, Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, China

Correspondence: Liu Jingjing, Email: yaowangdick{at}gmail.com

Abstract

Previous studies demonstrated that the elevated expression and receptor binding of gastrin-releasing peptide (GRP) in various types of cancer suggest that GRP might be a putative target for immunotherapy in neoplastic diseases. DNA vaccine for hormone/growth factor immune deprivation represents a feasible and attractive approach for cancer treatment; nevertheless, there is still a need to increase the potency of DNA vaccine. Here, based on 6 copies of the B cell epitope GRP18-27 in linear alignment as immunogen, we designed several anti-GRP DNA vaccines containing different combination of immunoadjuvants, such as HSP65, tetanus toxoid830-844 (T), pan HLA-DR-binding epitope (PADRE) (P), and mycobacterial HSP70407-426 (M), on a backbone of pCR3.1 plasmid vector with eight 5’-GACGTT-3’ CpG motifs and the VEGF183 signal peptide (VS). The effects of immunoadjuvants in enhancing GRP-specific humoral immune response were then evaluated by comparing the immunogenicity and antitumor effects. Immunization of mice with pCR3.1-VS-HSP65-TP-GRP6-M2 elicited much higher levels of specific anti-GRP antibodies and more effectively inhibited the growth of a GRP-dependent tumor RM-1 in vivo. Interestingly, plasmid encoding for 2 HSP70407-426, but not the one with 1 or 3 HSP70407-426 showed stronger immune stimulatory potential as well as impressive antitumor activity, suggesting that 2HSP70407-426 is an efficient molecular adjuvant for developing self-epitope vaccines. The highly immunogenic and potent anti-tumorigenic as well as antiangiogenesis activities of the anti-GRP DNA vaccine offered a novel immunotherapeutic approach in the treatment of the GRP-dependent tumor and its complications.