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 journalArticlepeer-review

8 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

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation funded by the Korean government (MSIP) (grant no. NRF-2017M3A9C8032204 , NRF-2015R1D1A1A09057154 and NRF-2015M3A9E6028949 ). This research was also partially supported by the New Drug Development Center, Asan Medical Center (2017-758).

Funding Information:
This work was supported by the National Research Foundation funded by the Korean government (MSIP) (grant no. NRF-2017M3A9C8032204, NRF-2015R1D1A1A09057154 and NRF-2015M3A9E6028949). This research was also partially supported by the New Drug Development Center, Asan Medical Center (2017-758).

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

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

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