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Immunological targeting of matrix metalloproteinase-9 as a novel approach to universal cancer vaccine: Characterization of anticancer antibodies efficacy in vitro

Chatterjee M, Ivanov V, Efremov E, Goc A, Niedzwiecki A, Rath M

WCRJ 2020; 7: e1499; DOI: 10.32113/wcrj_20203_1499

 

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 ma-trix 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 af-fordable 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.

Materials and Methods: The antibodies against mouse and rat MMP-9 oligopeptides were isolated and their effects on cancer cell invasion through Matrigel were tested individually and in combinations. Binding to the corresponding MMP sequences was evaluated by Western blot.

Results: All tested antibodies inhibited migration of both murine and human cancer cell lines: Human Prostate Cancer (DU145), Mouse Breast cancer (4T1) and Human Pancreas Carcinoma (MIA PaCa-2). The combination of these antibodies had enhanced effect on inhibiting cancer cells invasion. Antibody binding to MMP-9 was shown for all but one of the tested antibodies by Western Blot.

Conclusion: Controlling matrix metalloproteinases (MMPs) is a powerful tool against metastasis - the most life-threatening aspect in all cancers. The in vitro efficacy of specific antibodies effective against MMP-9 was elucidated in this study. We showed that specific anti-MMP-9 antibodies inhibit extracellular matrix invasion of different types of cancer cells and confirmed their binding to corresponding MMP-9 peptides. Enhanced efficacy of these immunogenic peptides was observed when used in a combination. These results urge further work in this direction with its goal of developing a universal anti-cancer vaccine.

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