GnRH and
VEGF have been investigated as prostate
carcinoma enhancers that support
tumor spread and progression. Although both have documented roles in prostate
carcinoma and many
cancer types, the weak immunogenicity of these
peptides has remained a major challenge for use in
immunotherapy. Here, we describe a novel strategy to inhibit
GnRH and
VEGF production and assess the effect on the immune responses against these
hormones using the RM-1
prostate cancer model. We designed a novel
recombinant fusion protein which combined
GnRH and
VEGF as a
vaccine against this
tumor. The newly constructed fusion
protein hVEGF121-M2-GnRH3-hinge-MVP contains the human
vascular endothelial growth factor (hVEGF121) and three copies of
GnRH in sequential linear alignment and T helper
epitope MVP as an immunogenic
vaccine. The effectiveness of the
vaccine in eliciting an immune response and attenuating the prostate
tumor growth was evaluated. Results showed that administration of a new
vaccine effectively elicited humoral and cellular immune responses. We found that, a novel fusion
protein, hVEGF121-M2-GnRH3-hinge-MVP, effectively inhibited growth of RM-1 prostate model and effectively promoted immune response. In conclusion, hVEGF121-M2-GnRH3-hinge-MVP is an effective dual mechanism
tumor vaccine that limits RM-1 prostate growth. This
vaccine may be a promising strategy for the treatment of
hormone refractory prostate
malignancies.