Abstract 4395: SEA technology: A novel strategy for enhancing antibody effector function

Abstract

Abstract The activity of monoclonal antibodies (mAbs) can be enhanced by a number of chemical and genetic strategies. We describe a novel strategy, Sugar Engineered Antibody (SEA) technology, for enhancing antibody-dependent cellular cytotoxicity (ADCC) through modification of the mAb carbohydrate. A series of small molecule fucose analogs were added to mAb-expressing Chinese hamster ovary (CHO) cells, with the resulting mAbs showing a significant reduction in their carbohydrate fucosylation. We demonstrate that these mAbs show markedly increased ADCC activity and improved CD16 binding. The fucose analogs inhibit GDP-mannose dehydratase (GMD), the first enzyme in de novo synthesis of GDP-fucose, and lead to global depletion of intracellular GDP-fucose. We also demonstrate that this strategy yields mAbs with significantly reduced fucosylation in large scale CHO cell culture and is broadly active across a variety of mAbs and expression systems. Since genetic modification of the mAb-producing cell line is not required, SEA technology can be readily applied from the mAb screening to manufacturing stage to generate effector function enhanced therapeutic antibodies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4395.