Efeitos do uso de dipeptídeos no cultivo de células CHO produtoras de anticorpo monoclonal

Abstract

The biopharmaceutical market has been growing steadily, thereby promoting the production of monoclonal antibodies for therapeutic purposes. As a consequence, the use of Chinese hamster ovary (CHO) cells, although already established, has been the focus of research in order to improve the production process. The use of dipeptides has been investigated as a promising proposal for supplementation of the culture medium, as they are metabolized slowly and potentially prevent the accumulation of ammonia in the medium, increasing both the productivity and the stability of the cells. In this project, CHO cells producing a monoclonal antibody were grown in a shaken flask in culture medium supplemented individually with dipeptides: alanyl-glutamine (AlaGln), glycyl-glutamine (GliGln), glycyl-tyrosine (GliTir) and acetyl-alanyl-glutamine (AcAlaGln), as possible glutamine substitutes. The effects of using these dipeptides were analyzed through a batch culture lasting 7 to 11 days. Cell growth, viability, productivity and concentration of substrates (glucose and glutamine) and byproducts (lactate and ammonia) were evaluated. Although the dipeptides increase the stability of cell culture and reduce the amount of lactate and ammonia produced, under the conditions of the experiments, it can be concluded that these molecules are not viable alternatives to the batch system to replace glutamine since they did not differ in the amount of monoclonal antibody produced.