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Hépato-Gastro & Oncologie Digestive

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Monoclonal antibodies: a major class of therapeutic drugs in gastrointestinal diseases Volume 19, issue 2, Février 2012

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Authors
Université François-Rabelais de Tours, CNRS, UMR 7292 (GICC), Service d’hépatogastroentérologie et de cancérologie digestive, CHRU de Tours, Hôpital Trousseau, 37044 Tours Cedex 9, CHRU de Tours, Hôpital Bretonneau, laboratoire d’immunologie, 37044 Tours Cedex 9, CHRU de Tours, Hôpital Bretonneau, laboratoire de pharmaco-toxicologie, 37044 Tours Cedex 9

Last ten years, therapeutic monoclonal antibodies have profoundly modified the treatment of a number of gastrointestinal diseases, such as colorectal cancer and inflammatory bowel diseases. The first monoclonal antibodies were of murine origin and had several drawbacks, notably low efficacy and immunogenicity. Thanks to the development of biotechnology, the human part of the antibody was indeed progressively increased, leading to chimeric, humanized and, finally, fully human monoclonal antibodies. Even if the development of monoclonal antibodies is a complex process, and if some of them may trigger worrying adverse effects, their contribution to therapeutics is major. Monoclonal antibody therapy, a form of passive immunotherapy, is clinically validated. Most therapeutic monoclonal antibodies are IgG1 isotype and they are naturally bi-functional molecules as endogenous IgG. They recognise their antigen through the variable regions of the antigen binding portion (Fab). The binding of a mAb to a soluble or a membrane antigen may interfere with one or several functions of this antigen, leading to the therapeutic effect. The Fc portion of therapeutic antibodies may have the ability to elicit effector mechanisms of the immune system, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC). At present, about twenty monoclonal antibodies are on the market, and a large number is under development.