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The human IgG3 subclass has the characteristics of high effect function and Fab arm flexibility. Here, the researchers used anti-CD20 IgG3 as a model to study the formation of IgG3 aggregates and the potential of such antibodies in treatment. The researchers swapped the constant domain of IgG3 with the constant domain of stable IgG1 to avoid a large number of aggregations of anti-CD20 IgG3 antibodies. The results showed that the collective formation of IgG3 antibodies with the IgG1 CH3 domain decreased. It was found that two amino acid mutations in the CH3 domain reduced the aggregation of IgG3 and increased the CH3 transition temperature. They improved the engineered human IgG3 antibody by further mutation and obtained IgG3KVH to achieve protein A binding and showed antigenic binding similar to that of wild-type IgG3. At the same time, IgG3KVH also has high binding activity to Fcγ RIIIa and C1q. In this study, the researchers obtained an engineered human IgG3 antibody with low aggregation, which will help to research and develop therapeutic antibodies with high effect function and Fab arm flexibility.
Saito, Seiji, et al. "A stable engineered human IgG3 antibody with decreased aggregation during antibody expression and low pH stress." Protein Science 28.5 (2019): 900-909. Distributed under Open Access license CC BY 4.0, without modification.
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