RESUMEN
Highlights of the 9th (Biennial) International Congress on TNF-Related Cytokines (30 October-2 November 2002; The Manchester Grand Hyatt, San Diego, CA, USA.
Asunto(s)
Glicoproteínas de Membrana , Proteínas de la Membrana , Receptores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa , Animales , Proteínas Reguladoras de la Apoptosis , Receptor del Factor Activador de Células B , Humanos , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/uso terapéutico , Receptores del Factor de Necrosis Tumoral/metabolismo , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Ligando Inductor de Apoptosis Relacionado con TNF , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.