(597d) Method for Improved Control of Anti-Tumor Effector Function of MAb By Modification of NS0 Cell Culture Medium

Fc effector function is a key anti-tumor mechanism of action for recombinant therapeutic monoclonal antibodies (mAbs).  In particular, antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells correlates directly with Fc binding of the mAb to the human CD16a receptor, which is in turn affected by the type of Fc N-linked glycan moiety.  More specifically, an increased level of a-fucosylated glycans (including mannosylated species) present on the mAb Fc, leads to increased Fc binding to CD16a receptor and enhanced ADCC activity.  This study investigated the effect of increased concentrations of the amino acid glycine in the chemically-defined culture media of NS0 murine cells engineered to express five different mAbs.  When cells were cultured in media with a 7-fold increase in glycine concentration, there was an increased prevalence of a-fucosylation and increased ADCC activity across all five monoclonal antibodies tested.  This study shows that elevated levels of glycine in cell culture media can be used to potentially improve the efficacy of possible therapeutic mAb candidates by enhancing ADCC and the Fc-directed killing of target tumor cells.