Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

Jae Seon Won, Pil Won Nam, Yong Chan Lee, Mu Hyeon Choe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recombinant antibody-toxins are constructed via the fusion of a "carcinoma-specific" antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G4S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]2) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalBiochemical and biophysical research communications
Volume382
Issue number1
DOIs
Publication statusPublished - 2009 Apr 24

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Keywords

  • Avidity
  • Cytotoxicity
  • Divalent antibody-toxin
  • Pseudomonas exotoxin A
  • Recombinant antibody refolding

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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