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.