Neutralizing monoclonal and chimeric antibodies to human interferon-gamma

作者：Larina M V^*; Aliev T K; Solopova O N; Pozdnyakova L P; Korobova S V; Yakimov S A; Sveshnikov P G; Dolgikh D A; Kirpichnikov M P

来源：Russian Journal of Bioorganic Chemistry, 2015, 41(3): 280-288.

DOI：10.1134/S106816201503005X

• interferon-gamma
• therapeutic monoclonal antibodies
• recombinant antibodies

Autoimmune diseases are chronic diseases characterized by abnormal immune response directed to the body's own antigens, which leads to tissue damage and violation of their normal functioning. These diseases often lead to disability and even death of patients. Nowadays, several monoclonal antibodies to proinflammatory cytokines and their receptors are used successfully for targeted therapy of autoimmune diseases. One of the most promising targets for the treatment of autoimmune diseases is the interferon-gamma (IFN-gamma), a key cytokine in Thl-cell differentiation, macrophage activation and inflammation. Five monoclonal antibodies (mAbs) to human IFN-gamma were produced in this work. Affinity of the antibodies to IFN-gamma and their ability to suppress the activity induced by IFN-gamma were studied in order to develop of a potential therapeutic agent. The mAb F1 was selected for chimerization based on the data of this study. The complex of mAb F1 with IFN-gamma had a dissociation constant of 1.7 nM; in addition, the antibody showed a low value of IC90 (8.9 +/- 2.0 nM) when suppressing IFN-gamma-induced HLA-DR antigen expression on the surface of the cell line U937. Bicistronic vector was designed for production of Fab-fragment of a chimeric antibody F1 chim in E. coli cells. The resulting recombinant chimeric Fab-fragment of F1 antibody neutralized IFN-gamma activity in vitro and had a dissociation constant of 1.8 nM.

• 出版日期2015-5