Matrix metalloproteinases-9 as a promising target for anti-cancer vaccine: inhibition of melanoma tumor growth in mice immunized with syngeneic MMP-9 peptides

Abstract

OBJECTIVE: The prevention and treatment of cancer remain a challenge. Current treatments are largely unsuccessful due to high toxicity. The most effective way to reduce global mortality from cancer is to block the initial stages of the disease, common to all types of cancer – invasion and metastasis. The elevated levels of matrix metalloproteinases, such as MMP-9 play a key role in tumorigenesis, angiogenesis, apoptosis, cancer invasion and metastasis. Among various therapeutic modalities, vaccines are the most effective and affordable approaches against diseases in general. In the global fight against cancer, a vaccine capable to impede MMP-2 and MMP-9 activity could open the door for effective prevention -- and even cure. We previously reported that mice immunized with synthetic oligopeptides containing specific amino acid sequences from human MMP-2 and MMP-9 showed a significant reduction in melanoma tumors and tumor burden. MATERIALS AND METHODS: Here, we tested a syngeneic approach to cancer vaccines by investigating whether immunization of mice with rodent derived MMP-9 oligopeptides would generate sufficient immune response and anticancer efficacy. Accordingly, C57Bl/6 mice were immunized with three oligopeptides containing specific sequences from rat MMP-9 and two oligopeptides from mouse MMP-9. All these peptides showed to be highly immunogenic in mice. RESULTS: Subsequently, the immunized mice challenged with B16FO melanoma cells developed significantly smaller tumors and had reduced tumor burden. The weight gain in vaccinated and control mice was comparable. In addition, no significant differences were observed in serum clinical chemistry, hematological parameters and the histopathology of major organs in relation to test peptides in the immunized mice. CONCLUSIONS: Our findings confirm that MMP peptide-based vaccines can be a viable strategy for cancer therapy.

Keywords

• cancer vaccine
• mmp-9
• immunogenic oligopeptides
• melanoma cancer
• tumor growth