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

JaeSeon Won, PilWon Nam, YongChan Lee, MuHyeon 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

Fingerprint

Cytotoxicity
Antibodies
Immunoglobulin Fragments
Monomers
Cells
Gonadotrophs
Immunotoxins
Exotoxins
Immunoglobulin Fab Fragments
Surface Antigens
Pseudomonas
Disulfides
Dimers
Cysteine
Tumors
Neoplasms
Fusion reactions
Monoclonal Antibodies
Carcinoma
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins. / Won, JaeSeon; Nam, PilWon; Lee, YongChan; Choe, MuHyeon.

In: Biochemical and Biophysical Research Communications, Vol. 382, No. 1, 24.04.2009, p. 15-20.

Research output: Contribution to journalArticle

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