Bispecific anti-mPDGFR beta x cotinine scFv-C-kappa-scFv fusion protein and cotinine-duocarmycin can form antibody-drug conjugate-like complexes that exert cytotoxicity against mPDGFR beta expressing cells
- 주제(키워드) Antibody-drug conjugate , Bispecific antibody , Cotinine , Duocarmycin
- 주제(기타) Biochemical Research Methods; Biochemistry & Molecular Biology
- 설명문(일반) [Kim, Soohyun; Chung, Junho] Seoul Natl Univ, Dept Biochem & Mol Biol, Coll Med, Seoul 00380, South Korea; [Kim, Soohyun; Chung, Junho] Seoul Natl Univ, Canc Res Inst, Coll Med, Seoul 00380, South Korea; [Kim, Hyori] Asan Med Ctr, Asan Inst Life Sci, Convergence Med Res Ctr, Seoul, South Korea; [Kim, Hyori] Univ Ulsan, Dept Convergence Med, Coll Med, Seoul, South Korea; [Jo, Dong Hyun; Kim, Jeong Hun] Seoul Natl Univ Hosp, Clin Res Inst, Fight Angiogenesis Related Blindness FARB Lab, Seoul, South Korea; [Kim, Jeong Hun; Hwang, Dobeen; Chung, Junho] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul 00380, South Korea; [Kim, Jeong Hun] Seoul Natl Univ, Dept Ophthalmol, Coll Med, Seoul, South Korea; [Kim, Su Ree; Kang, Dongmin] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 ACADEMIC PRESS INC ELSEVIER SCIENCE
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160079
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.ymeth.2018.10.002
- PubMed https://pubmed.ncbi.nlm.nih.gov/30292795
초록/요약
Antibody selection for antibody-drug conjugates (ADCs) has traditionally depended on its internalization into the target cell, although ADC efficacy also relies on recycling of the receptor-ADC complex, endo-lysosomal trafficking, and subsequent linker/antibody proteolysis. In this study, we observed that a bispecific anti-murine platelet-derived growth factor receptor beta (mPDGFR beta) x cotinine single-chain variable fragment (scFv)-kappa constant region (C-kappa)-scFv fusion protein and cotinine-duocarmycin can form an ADC-like complex to induce cytotoxicity against rnPDGFR beta expressing cells. Multiple anti-mPDGFR beta antibody candidates can be produced in this bispecific scFv-C-kappa-scFv fusion protein format and tested for their ability to deliver cotinine-conjugated cytotoxic drugs, thus providing an improved approach for antibody selection in ADC development.
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