Factors Influencing mAb Aggregation in Mammalian Cell Culture
Poster Sep 24, 2014
Albert Paul, Melanie Leitte, Franziska Schandock, Rene Handrick and Friedemann Hesse
Monoclonal antibodies (mAbs) are important biopharmaceuticals for the treatment of many diseases. During manufacturing the proteins tend to form aggregates, which reduce product yields, influence drug performance and safety. Environmental conditions during production in mammalian cell culture influence the formation of high molecular weight (HMW) species. In this report, we show how mAb aggregates can be detected directly in the cell culture supernatant using size exclusion chromatography (SEC) in a high pressure liquid chromatography (HPLC) system. We have investigated the impact of batch cultivation in different culture vessels, the addition of Valproic acid (VPA) as small molecule enhancer of protein production and the influence of the cell culture environment itself on the formation of mAb aggregates in Chinese hamster ovary (CHO) cell culture. Our results prove that aggregate formation can occur already during upstream processing (USP) due to intracellular and extracellular mechanisms and is not only a problem in downstream processing (DSP).
Spinal muscular atrophy (SMA) is an inheritable cause of infant mortality that is characterized by the loss of lower motor neurons and skeletal muscle atrophy. The degeneration of motor neurons is caused by insufficient levels of survival motor neuron (SMN) protein, which is encoded by two nearly identical genes SMN1 and SMN2. Most cases of SMA harbour homozygous deletions of the SMN1 gene and retain at least one copy of SMN2.READ MORE