Effect of Process Parameters on the Formation of Anti-CD3 and Claudin 18.2 Bispecific Antibody Aggregates
In recent years,with the successful marketing of a variety of bispecific antibody drugs and the development of genetic engineering technology,bispecific antibody has become a popular research topic in the antibody field.Due to the complex structure of bispecific antibodies,aggregates are often more likely to form during the manufacturing process,which not only increases the difficulty of downstream purification,but also increases the cost of experiments.In order to reduce bispecific antibody aggregates in the production process,CHO cells expressing anti-CD3 and Claudin 18.2 bispecific antibodies were used as the research object.Design of experiment(DOE)approach was used in a 2 L bioreactor to investigate the influence of various process parameters on the formation of aggregates during the production of CD3 and Claudin 18.2 bispecific antibodies.The model between process parameters and aggregate content was established,the control range of optimized process parameters was determined,and the optimized process conditions were verified in a 200 L bioreactor.The results of the DOE approach show that pH,feed concentration and carbon source concentration have significant and negative effects on aggregate formation.When the pH is 7.0-7.2,the feed concentration is 5.5％,and the carbon source concentration is 8-10 g/L,the verification results in the 200 L bioreactor show that the aggregate content is(27.62±4.55)％,which is consistent with the results predicted by the model.
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