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This Article Full Text Full Text (PDF) All Versions of this Article: ERC-09-0058v1 16/4/1171    most recent 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lu, Y. Articles by Liu, J. Search for Related Content PubMed PubMed Citation Articles by Lu, Y. Articles by Liu, J.

¹ Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, People's Republic of China
² Shanghai Yijiu Biomedical Cooperation Ltd, Shanghai Zhangjiang Hi-Tech Park, Shanghai 210009, People's Republic of China

(Correspondence should be addressed to L Jingjing; Email: minigene1{at}21cn.com)

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 the DNA vaccine. Here, based on six copies of the B cell epitope GRP_18–27 in a linear alignment as an immunogen, we designed several anti-GRP DNA vaccines containing different combinations of immunoadjuvants, such as HSP65, tetanus toxoid_830–844 (T), pan HLA-DR-binding epitope (PADRE) (P), and mycobacterial HSP70_407–426 (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 these immunoadjuvants in enhancing GRP-specific humoral immune response were then evaluated by comparing the respective 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, plasmids encoding for 2HSP70_407–426, but not the one with 1 or 3HSP70_407–426 showed stronger immune stimulatory potential as well as impressive antitumor activity, suggesting that 2HSP70_407–426 is an efficient molecular adjuvant for developing self-epitope vaccines. The highly immunogenic, potent anti-tumorigenic and antiangiogenesis activities of the anti-GRP DNA vaccine offered a novel immunotherapeutic approach in the treatment of GRP-dependent tumors and their complications.