RESUMEN
Tumor necrosis factor (TNF) is a proinflammatory cytokine implicated in pathogenesis of multiple autoimmune and inflammatory diseases. Anti-TNF therapy has revolutionized the therapeutic paradigms of autoimmune diseases and became one of the most successful examples of the clinical use of monoclonal antibodies. Currently, anti-TNF therapy is used by millions of patients worldwide. At the moment, fully human anti-TNF antibody Adalimumab is the best-selling anti-cytokine drug in the world. Here, we present a story about a highly potent anti-TNF monoclonal antibody initially characterized more than 20 years ago and further developed into chimeric and humanized versions. We present comparative analysis of this antibody with Infliximab and Adalimumab.
Asunto(s)
Adalimumab/biosíntesis , Anticuerpos Monoclonales Humanizados/biosíntesis , Anticuerpos Monoclonales/biosíntesis , Artritis Reumatoide/tratamiento farmacológico , Infliximab/biosíntesis , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/aislamiento & purificación , Adalimumab/farmacología , Animales , Antiinflamatorios no Esteroideos , Anticuerpos Monoclonales/historia , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados/historia , Anticuerpos Monoclonales Humanizados/aislamiento & purificación , Anticuerpos Monoclonales Humanizados/farmacología , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Clonación Molecular , Expresión Génica , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Infliximab/aislamiento & purificación , Infliximab/farmacología , Ratones , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Psoriasis/inmunología , Psoriasis/patología , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/inmunología , Espondilitis Anquilosante/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Production of monoclonal antibodies and pharmaceutical proteins in transgenic plants has been the focus of many research efforts for close to 30 years. Use of plants as bioreactors reduces large-scale production costs and minimizes risk for human pathogens contamination. Stable nuclear transformation of the plant genome offers a clear advantage in agricultural protein production platforms, limited only by the number of hectares that can be cultivated. We report here, for the first time, successful and stable expression of adalimumab in transgenic Nicotiana tabacum plants. The plant-derived adalimumab proved fully active and was shown to rescue L929 cells from the in vitro lethal effect of rhTNFα just as effectively as commercially available CHO-derived adalimumab (Humira). These results indicate that agricultural biopharming is an efficient alternative to mammalian cell-based expression platforms for the large-scale production of recombinant antibodies.