期刊
METHODS
卷 154, 期 -, 页码 125-135出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymeth.2018.10.002
关键词
Antibody-drug conjugate; Bispecific antibody; Cotinine; Duocarmycin
资金
- National Research Foundation - Korean government (MSIP) [NRF-2017M3A9C8032204, NRF-2015R1D1A1A09057154, NRF-2015M3A9E6028949]
- New Drug Development Center, Man Medical Center [2017-758]
- National Research Foundation of Korea [2017M3A9C8032204] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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