Anti-EGFR scFv tetramer (tetrabody) with a stable monodisperse structure, strong anticancer effect, and a long in vivo half-life

Ryutaro Asano, Noriaki Koyama, Yasuyo Hagiwara, Yosuke Masakari, Ryota Orimo, Kyoko Arai, Hiromi Ogata, Shozo Furumoto, Mitsuo Umetsu, Izumi Kumagai

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The development of single-chain variable fragments (scFvs) as therapeutic agents has the potential to reduce the high cost of antibody production, but the development process often impairs scFv functions such as binding affinity and pharmacokinetics. Multimerization is one strategy for recovering or enhancing these lost functions. Previously, we constructed several antiepidermal growth factor receptor (EGFR) scFv multimers by modifying linker length and domain order. Antitumor effects comparable with those of the currently approved anti-EGFR therapeutic antibodies were observed for scFv trimers. In the present study, we fractionated an anti-EGFR scFv tetramer from the intracellular soluble fraction of an Escherichia coli transformant. Compared with the trimer, the tetramer showed higher affinity, greater cancer cell growth inhibition, and prolonged blood retention time. Furthermore, the tetramer did not dissociate into the trimer or other smaller species during long-term storage (up to 33 weeks). Thus, our developed scFv tetramer is an attractive candidate next-generation anti-EGFR therapeutic antibody that can be produced via a low-cost bacterial expression system.

Original languageEnglish
Pages (from-to)594-602
Number of pages9
JournalFEBS Open Bio
Volume6
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Keywords

  • Anticancer effect
  • EGFR
  • ScFv
  • ScFv multimer
  • Tetrabody

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Anti-EGFR scFv tetramer (tetrabody) with a stable monodisperse structure, strong anticancer effect, and a long in vivo half-life'. Together they form a unique fingerprint.

Cite this