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Peptide vaccines directed against human Metalloproteinases (MMPs) with anti-tumor efficacy in vitro and in vivo

M.W. Roomi, Ph.D., A. Niedzwiecki, Ph.D., M. Rath, M.D.

Dr. Rath Research Institute,  1260 Memorex Drive, Santa Clara, CA 95050

Journal of Cellular Medicine and Natural Health

Abstract: 

Despite sporadic progress, cancer has thus far eluded preventive and therapeutic approaches that can lead to an effective control of this global epidemic. The single most important reason for this failure is the fact that no effective intervention became available to impede the pathological pathways common to all types of cancer. In our study, we targeted metalloproteinases (MMPS), endopeptidases that are involved in the breakdown of extracellular matrix (ECM). Among them, MMP-2 and MMP-9 are critically involved in all stages of cancer development including tumor growth, invasion and metastasis.

Our goal was to develop an anti-cancer vaccine by inhibiting these specific enzymes. We selected three oligopeptides from human MMP-9 and one from human MMP-2. We demonstrated the efficacy of these oligopeptides in generating immune response in mice. The  in vitro tests showed that anti-MMPs sera were effective in curbing invasion of HeLA cells through the extracellular matrix system (Matrigel).

In our in vivo studies, we tested these oligopeptides for efficacy and safety in mice challenged with melanoma B16FO cells. All immunized animals injected with melanoma cancer cells grew smaller tumors than the control mice. The weight of tumors developed in the immunized animals was only about 30% of the controls, signifying a dramatic inhibition of tumor growth.  The reduction in tumor volume varied between the peptide vaccines, but on average was even more pronounced. The highest reduction of tumor volume compared to control was 88% achieved with a vaccine derived from the human MMP-2 oligopeptide, followed by a reduction of 80% with one of the human MMP-9 oligopeptides. The weight gain of vaccinated and control animals was comparable throughout the study and no pathological side-effects were observed in the vaccinated animals.

If confirmed by further in vivo and later clinical studies, a vaccine for the prevention and treatment of all types of cancers – irrespective of their origin and type – may become available. Moreover, the limited economic burden of such a vaccine approach would allow its world-wide implementation towards the global control of cancer.

Key words: cancer vaccine, melanoma B16FO, human MMPs peptides, MMP2, MMP9, tumor growth, immune response, HeLa, cancer invasion

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