Recent Achievements and Challenges in Prolonging the Serum Half-Lives of Therapeutic IgG Antibodies Through Fc Engineering
- Authors
- Ko, Sanghwan; Jo, Migyeong; Jung, Sang Taek
- Issue Date
- 3월-2021
- Publisher
- ADIS INT LTD
- Citation
- BIODRUGS, v.35, no.2, pp.147 - 157
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIODRUGS
- Volume
- 35
- Number
- 2
- Start Page
- 147
- End Page
- 157
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/128459
- DOI
- 10.1007/s40259-021-00471-0
- ISSN
- 1173-8804
- 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 in vitro techniques to determine the equilibrium binding constants and instantaneous rate constants for pH-dependent FcRn binding, but also diverse in vivo animal models including wild-type mouse, human FcRn transgenic mouse (Tg32 and Tg276), humanized mouse (Scarlet), or cynomolgus monkey have been harnessed. Currently, multiple IgG Fc variants that have been validated for their prolonged therapeutic potency in preclinical models have been successfully entered into human clinical trials for cancer, infectious diseases, and autoimmune diseases.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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