Engineered aglycosylated full-length IgG Fc variants exhibiting improved Fc gamma RIIIa binding and tumor cell clearance
- Authors
- 정상택
- Issue Date
- 1월-2018
- Publisher
- TAYLOR FRANCIS INC
- Keywords
- Aglycosylated IgG; Antibody-dependent cell-mediated cytotoxicity; Effector functions; Fc engineering; Fc gamma RIIIa
- Citation
- MABS, v.10, no.2, pp.278 - 289
- Indexed
- SCIE
SCOPUS
- Journal Title
- MABS
- Volume
- 10
- Number
- 2
- Start Page
- 278
- End Page
- 289
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/139797
- DOI
- 10.1080/19420862.2017.1402995
- ISSN
- 19420862
- Abstract
- Fc gamma RIIIa, which is predominantly expressed on the surface of natural killer cells, plays a key role in antibody-dependent cell-mediated cytotoxicity ( ADCC), a major effector function of therapeutic IgG antibodies that results in the death of aberrant cells. Despite the potential uses of aglycosylated IgG antibodies, which can be easily produced in bacteria and do not have complicated glycan heterogeneity issues, they show negligible binding to FcgRIIIa and abolish the activation of immune leukocytes for tumor cell clearance, in sharp contrast to most glycosylated IgG antibodies used in the clinical setting. For directed evolution of aglycosylated Fc variants that bind to FcgRIIIa and, in turn, exert potent ADCC effector function, we randomized the aglycosylated Fc region of full-length IgG expressed on the inner membrane of Escherichia coli. Multiple rounds of high-throughput screening using flow cytometry facilitated the isolation of aglycosylated IgG Fc variants that exhibited higher binding affinity to Fc gamma RIIIa-158V and Fc gamma RIIIa-158F compared with clinical-grade trastuzumab (Herceptin (R)). The resulting aglycosylated trastuzumab IgG antibody Fc variants could elicit strong peripheral blood mononuclear cell-mediated ADCC without glycosylation in the Fc regio
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.