Recent Achievements and Challenges in Prolonging the Serum Half-Lives of Therapeutic IgG Antibodies Through Fc Engineering.

ABSTRACT: Association of FcRn molecules to the Fc region of IgG in acidified endosomes and subsequent dissociation of the interaction in neutral pH serum enables IgG molecules to be recycled for prolonged serum persistence after internalization by endothelial cells, rather than being degraded in the serum and in the lysosomes inside the cells. Exploiting this intracellular trafficking and recycling mechanism, many researchers have engineered the Fc region to further extend the serum half-lives of therapeutic antibodies by optimizing the pH-dependent IgG Fc-FcRn interaction, and have generated various Fc variants exhibiting significantly improved circulating half-lives of therapeutic IgG antibodies. In order to estimate pharmacokinetic profiles of IgG Fc variants in human serum, not only a variety of

SUBMITTER: Ko S 

PROVIDER: S-EPMC7894971 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature