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Biochemistry Research International
Volume 2011, Article ID 191670, 11 pages
http://dx.doi.org/10.1155/2011/191670
Review Article

New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

1Merck Serono S.A., 9 Chemin des Mines, Case postale 54, 1211 Geneva 20, Switzerland
2Cell Biology and Translational Research, Dyax Corp., 300 Technology Square, Cambridge, MA 02139, USA

Received 27 May 2010; Accepted 4 September 2010

Academic Editor: David N. Brindley

Copyright © 2011 Laetitia Devy and Daniel T. Dransfield. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

MMP intervention strategies have met with limited clinical success due to severe toxicities. In particular, treatment with broad-spectrum MMP-inhibitors (MMPIs) caused musculoskeletal pain and inflammation. Selectivity may be essential for realizing the clinical potential of MMPIs. Here we review discoveries pinpointing membrane-bound MMPs as mediators of mechanisms underlying cancer and inflammation and as possible therapeutic targets for prevention/treatment of these diseases. We discuss strategies to target these therapeutic proteases using highly selective inhibitory agents (i.e., human blocking antibodies) against individual membrane-bound MMPs.