A monoclonal antibody that neutralizes an heterogeneous collection of hIFN-alpha

DEPETRIS, M.; OGGERO EBERHARDT, M.; KRATJE, R. B.; ETCHEVERRIGARAY, M.

Pinamar. Pcia. Buenos Aires

Congreso; X Congreso de la Panamerican Association of Biochemistry and Molecular Biology (PABMB) ? XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB) ? XX Reunión Anual de la Sociedad Argentina de Neuroquímica; 2005

Panamerican Association of Biochemistry and Molecular Biology; Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; Sociedad Argentina de Neuroquímica

Increased expression of human interferon alpha (hIFN-alfa) correlates with acute viral infections, inflammatory disorders and several autoimmune illnesses where the cytokine may be a component of either initiating or maintaining the disease. Nowadays, the therapeutic use of monoclonal antibodies (mAbs) has gained acceptance, representing IFN-alfa an attractive target for antibody based therapy. A panel of 11 murine mAbs was prepared using recombinant hIFN alfa2b. Taking into account the affinity constant, the inhibition of IFN-alfa biological activity and the recognition of different molecular areas of the cytokine, four mAbs were selected to produce scFv fragments. One of these fragments (CA5E6) was able to neutralize a wide spectrum of IFN alfas including the recombinant human cytokines IFN alfa2a and IFN alfa2b and an heterogeneous collection of IFN alfas produced by activated leukocytes and Namalwa cells (lymphoblastoid IFN). On the other hand, binding experiments showed a very low decrease in scFv affinity in comparison with the parent murine antibody. Consequently, having established the ability of scFv CA5E6 to neutralize a broad diversity of IFN-alfas, it is a potential candidate to be used for the treatment of diseases such as systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis.