Isolation and characterization of human monoclonal antibodies specific to MMP-1A, MMP-2 and MMP-3

Experimental Cell Research
Stefanie PfaffenDario Neri

Abstract

Matrix metalloproteinases (MMPs), a group of more than 20 zinc-containing endopeptidases, are up-regulated in many diseases, but the use of MMP inhibitors for therapeutic purposes has often been disappointing, possibly for the limited specificity of the drugs used in clinical trials. In principle, individual MMPs could be specifically drugged by monoclonal antibodies, either by inhibition of their catalytic activity or by antibody-based pharmacodelivery strategies. In this article we describe the isolation and affinity maturation of recombinant antibodies (SP1, SP2, SP3) specific to the murine catalytic domains of MMP-1A, MMP-2 and MMP-3. These novel reagents allowed a systematic comparative immunofluorescence analysis of the expression patterns of their cognate antigens in a variety of healthy, cancerous and arthritic murine tissues. While all three MMPs were strongly expressed in tumor and arthritis specimens, MMP-1A was completely undetectable in the normal tissues tested, while MMP-2 and MMP-3 exhibited a weak expression in certain normal tissues (e.g., liver). The new antibodies may serve as building blocks for the development of antibody-based therapy strategies in mouse models of pathology.

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Citations

Apr 21, 2010·European Journal of Nuclear Medicine and Molecular Imaging·Stefanie PfaffenDario Neri
Apr 17, 2014·Journal of Cellular Physiology·Caitlin J Foley, Athan Kuliopulos
Mar 1, 2016·Scientific Reports·Kranthi Marella PanthPhilippe Lambin
Feb 22, 2012·Biochemical and Biophysical Research Communications·Anna Cyranka-CzajaJacek Otlewski
May 18, 2010·Biochimie·Marie-Louise Zani, Thierry Moreau
Mar 3, 2015·Current Opinion in Chemical Biology·Florent Samain, Giulio Casi
Jun 22, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Maxim LevinIrit Sagi
Sep 29, 2011·Arthritis and Rheumatism·Panagiotis KamperidisCostantino Pitzalis
May 11, 2012·The Journal of Biological Chemistry·Caitlin J FoleyAthan Kuliopulos
Jun 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zheng-Hua Wang, Hu Zhan-Sheng

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