Bispecific anti-mPDGFRβ x cotinine scFv-Cκ-scFv fusion protein and cotinine-duocarmycin can form antibody-drug conjugate-like complexes that exert cytotoxicity against mPDGFRβ expressing cells

Soohyun Kim, Hyori Kim, Dong Hyun Jo, Jeong Hun Kim, Su Ree Kim, Dongmin Kang, Dobeen Hwang, Junho Chung

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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 (mPDGFRβ) x cotinine single-chain variable fragment (scFv)-kappa constant region (Cκ)-scFv fusion protein and cotinine-duocarmycin can form an ADC-like complex to induce cytotoxicity against mPDGFRβ expressing cells. Multiple anti-mPDGFRβ antibody candidates can be produced in this bispecific scFv-Cκ-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.

Original languageEnglish
Pages (from-to)125-135
Number of pages11
JournalMethods
Volume154
DOIs
StatePublished - 1 Feb 2019

Keywords

  • Antibody-drug conjugate
  • Bispecific antibody
  • Cotinine
  • Duocarmycin

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