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

Objective: Therapeutic approach to cancer based on a vaccine targeting various types of cancer compared to being cancer-type specific has many advantages and can be applied to large population. Our previous in vivo studies demonstrated that a vaccine aimed at curbing cancer metastasis by inhibiting matrix metalloproteinases (MMPs) – Matrix Metalloproteinase -2 (MMP-2) and Matrix Metalloproteinase -9 (MMP-9) - has potential in preventing cancer. This study investigated mechanical aspects of anti-MMP-9 antibodies with previously documented anti-cancer efficacy in vivo, for inhibition of cancer cell migration and their binding efficacy. 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. Conclusions: 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.

Abstract licence: CC BY-NC-SA

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