THE GLYCOSYLATION OF A CHIMERIC anti-rhIFN-α2b ANTIBODY PRODUCED IN DIFFERENT CELL LINES INFLUENCES ITS NEUTRALIZING ACTIVITY

ATTALLAH, C; AGUILAR, MF; ETCHEVERRIGARAY, M; OGGERO, M

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS

The monoclonal antibodies constitute a large subset of the marketed biotherapeutics, most of which are glycosylated, and thus produced in mammalian cells. These molecules are bifunctionals, since the variable (V) regions are responsible of antigen binding and the constant (C) regions confer effector properties. However, this immunological dogma is in revision because several studies suggest that C regions of different class or subclasses of antibodies with identical V regions, influence the antigen binding activity Also, despite the glycosylation pattern strongly influences the antibody effector functions, this feature always was considered not to be important for binding antigen ability. In this work, we studied the impact of the different cell lines on the the affinity constant and antigen neutralizing ability of a chimeric anti hIFN α2b murine single chain Fv fused to Fc1 (scFv Fc). The proteins, produced by CHO K1, HEK293 and NS0 cells showed no significant differences in the affinity constant measured by competitive ELISA. In spite of this parameter, the in vitro IFN neutralizing ability of the antibodies was higher for the molecule produced by CHO cells. In fact, the neutralizing activity of the same deglycosylated protein was considerably reduced. The present study invites us to critically discuss the choice of the cell line to produce biotherapeutic antibodies.