Engineering the hinge region of human IgG1 Fc-fused bispecific antibodies to improve fragmentation resistance.

ABSTRACT: Fc domain fusion can improve the therapeutic effects of relatively small biological molecules such as peptides, cytokines, and antibody fragments. Fc fusion proteins can also be used to enhance the cytotoxic effects of small bispecific antibodies (bsAbs). However, fragmentation of Fc fusion proteins, which mainly occurs around the hinge regions during production, storage, and circulation in the blood, is a major issue. In this study, we first investigated the mechanisms of fragmentation around the hinge region during storage using Fc-fused bsAbs with specificity for epidermal growth factor receptor and CD3 as a model. The fragmentation peaks generated by gel filtration analysis indicated that both contaminating proteases and dissolved active oxygen should be considered causes of fragmentat

SUBMITTER: Suzuki S 

PROVIDER: S-EPMC6250740 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature