HYPERGLYCOSYLATED INTERFERON-ALPHA PRODUCED IN CHO-K1 AND HEK293 CELLS: DIFFERENCES IN GLYCAN STRUCTURE, BIOLOGICAL ACTIVITY AND PHARMACOKINETICS

GUGLIOTTA, AGUSTINA; RAUD, BRENDA; OGGERO, MARCOS; ETCHEVERRIGARAY, MARINA; KRATJE, RICARDO; CEAGLIO, NATALIA

Barcelona

Congreso; 24th Meeting of the European Society for Animal Cell Technology (ESACT); 2015

European Society for Animal Cell Technology (ESACT)

Glycosylation is one of the most important post-translational modifications that proteins can undergo because it defines their biological and physicochemical characteristics. Even though oligosaccharide structures attached to proteins are conserved among eukaryotes, many differences have been found between therapeutic glycoproteins expressed in different hosts.Chinese Hamster Ovary (CHO) cells are the most commonly used mammalian hosts for the production of commercially approved biopharmaceuticals. Human Embryonic Kidney (HEK) cells have gained importance due to their ability to produce glycoproteins that are very similar to the human naturally secreted proteins in terms of post-translational modifications, specifically glycosylation. Another advantage is that this system avoids the expression of antigenic glycoforms like N-glycolylneuraminic acid (Neu5Gc) present in CHO derived products. For these reasons, there is an increasing interest in using human cell lines for the production of recombinant therapeutic proteins.The benefits demonstrated by IFN4N prompted us to develop CHO-K1 and HEK 293 producer cell lines in order to investigate the differences in the carbohydrate composition of both products as well as its influence on their biological activity and pharmacokinetic properties.