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Establishing efficient protocols and platforms for the obtainment of monoclonal biosimilar with a commercial interest: recombinant monoclonal antibodies anti-TNFa as a development model

Abstract

Antibodies are glycoproteins produced by plasma cells, the IgG the most commonly used in antibody therapy. Hybridoma technology has enabled the production of monoclonal antibodies (mAbs) derived from laboratory animals. Methods as phage display allowed the development of recombinant antibody fragments (rAbs), with in vitro immunological repertoires without direct immunization of living hosts. After FDA first approval, mAbs have become the largest therapeutic agents studied against a variety of human diseases, generating an overall annual income of over $ 150 billion, with double the success rates of approval than other molecules. In 2002, adalimumab (Humira) was the first Phage-derived therapeutic mAb obtained, approved, and commercialized, thus the most successful molecule on the market and prescribed for a wide variety of immune-mediated disorders. Its target is a proinflammatory molecule, tumor necrosis factor (TNF), which plays a central role in the beginning and perpetuation of inflammatory processes in chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, ulcerative colitis, among others. The anti-TNF drug classes are the most profitable molecules globally, however, the costs are driven mainly by high health care costs and the final product price. Most commercial mAbs are obtained either from mammalian cells or hybridomas by pharmaceutical companies located outside Latin America. The microbial expression system in Escherichia coli is a faster and low-cost alternative applied for the production of these molecules as it has been used in the production of recombinant proteins on a large scale. Certolizumab (Cimzia) is the only available anti-TNF that utilizes this expression platform. In this scenario and inserted in a biotechnological context, the aim of the present project is to establish a platform for the generation of biosimilars and improved recombinant antibodies based on anti-TNF mAbs, targeting cost reduction, national and Latin American market. (AU)