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Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo
Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target prote...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384954/ https://www.ncbi.nlm.nih.gov/pubmed/22754528 http://dx.doi.org/10.3389/fphar.2012.00122 |
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author | Lund, Ida K. Rasch, Morten G. Ingvarsen, Signe Pass, Jesper Madsen, Daniel H. Engelholm, Lars H. Behrendt, Niels Høyer-Hansen, Gunilla |
author_facet | Lund, Ida K. Rasch, Morten G. Ingvarsen, Signe Pass, Jesper Madsen, Daniel H. Engelholm, Lars H. Behrendt, Niels Høyer-Hansen, Gunilla |
author_sort | Lund, Ida K. |
collection | PubMed |
description | Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target protein function(s). This approach has the advantage of being a model for therapeutic targeting. mAbs for use in mouse models can be obtained through immunization of gene-deficient mice with the autologous protein. Such mAbs react with both species-specific epitopes and epitopes conserved between species. mAbs against proteins involved in extracellular proteolysis, including plasminogen activators urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA), their inhibitor PAI-1, the uPA receptor (uPAR), two matrix metalloproteinases (MMP9 and MMP14), as well as the collagen internalization receptor uPARAP, have been developed. The inhibitory mAbs against uPA and uPAR block plasminogen activation and thereby hepatic fibrinolysis in vivo. Wound healing, another plasmin-dependent process, is delayed by an inhibitory mAb against uPA in the adult mouse. Thromboembolism can be inhibited by anti-PAI-1 mAbs in vivo. In conclusion, function-blocking mAbs are well-suited for targeted therapy in mouse models of different diseases, including cancer. |
format | Online Article Text |
id | pubmed-3384954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33849542012-07-02 Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo Lund, Ida K. Rasch, Morten G. Ingvarsen, Signe Pass, Jesper Madsen, Daniel H. Engelholm, Lars H. Behrendt, Niels Høyer-Hansen, Gunilla Front Pharmacol Pharmacology Identification of targets for cancer therapy requires the understanding of the in vivo roles of proteins, which can be derived from studies using gene-targeted mice. An alternative strategy is the administration of inhibitory monoclonal antibodies (mAbs), causing acute disruption of the target protein function(s). This approach has the advantage of being a model for therapeutic targeting. mAbs for use in mouse models can be obtained through immunization of gene-deficient mice with the autologous protein. Such mAbs react with both species-specific epitopes and epitopes conserved between species. mAbs against proteins involved in extracellular proteolysis, including plasminogen activators urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA), their inhibitor PAI-1, the uPA receptor (uPAR), two matrix metalloproteinases (MMP9 and MMP14), as well as the collagen internalization receptor uPARAP, have been developed. The inhibitory mAbs against uPA and uPAR block plasminogen activation and thereby hepatic fibrinolysis in vivo. Wound healing, another plasmin-dependent process, is delayed by an inhibitory mAb against uPA in the adult mouse. Thromboembolism can be inhibited by anti-PAI-1 mAbs in vivo. In conclusion, function-blocking mAbs are well-suited for targeted therapy in mouse models of different diseases, including cancer. Frontiers Research Foundation 2012-06-28 /pmc/articles/PMC3384954/ /pubmed/22754528 http://dx.doi.org/10.3389/fphar.2012.00122 Text en Copyright © 2012 Lund, Rasch, Ingvarsen, Pass, Madsen, Engelholm, Behrendt and Høyer-Hansen. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Pharmacology Lund, Ida K. Rasch, Morten G. Ingvarsen, Signe Pass, Jesper Madsen, Daniel H. Engelholm, Lars H. Behrendt, Niels Høyer-Hansen, Gunilla Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo |
title | Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo |
title_full | Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo |
title_fullStr | Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo |
title_full_unstemmed | Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo |
title_short | Inhibitory Monoclonal Antibodies against Mouse Proteases Raised in Gene-Deficient Mice Block Proteolytic Functions in vivo |
title_sort | inhibitory monoclonal antibodies against mouse proteases raised in gene-deficient mice block proteolytic functions in vivo |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384954/ https://www.ncbi.nlm.nih.gov/pubmed/22754528 http://dx.doi.org/10.3389/fphar.2012.00122 |
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