Diphtheria Toxin-Epidermal Growth Factor Fusion Protein and Pseudomonas Exotoxin-Interleukin 13 Fusion Protein Exert Synergistic Toxicity against Human Glioblastoma Multiforme Cells

Tie Fu Liu, Mark C. Willingham, Stephen B. Tatter, Kimberley A. Cohen, A. Corinne Lowe, Andrew Thorburn, Arthur E. Frankel

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The cytotoxicity of combinations of a diphtheria toxin-human epidermal growth factor fusion protein (DAB389EGF) and a Pseudomonas exotoxin-human interleukin 13 fusion protein (IL13PE38QQR) was tested against 14 human glioma cell lines. After cells were cultured for 48 h with various concentrations of the fusion proteins, the percentage reductions in thymidine incorporation were determined. Seven of fourteen cell lines were highly sensitive to DAB389EGF alone, and six cell lines were highly sensitive to IL13PE38QQR alone with IC90's < 100 pM. When combined, synergistic cell killing was observed for seven of the cell lines based upon concave isobolograms and combination indices (CI's) of 0.2 to 0.7. Supraadditive cytotoxicity was confirmed by measurements of induction of apoptosis. Receptor expression was assessed by flow cytometry and confocal microscopy. Marked heterogeneity of expression of EGFR and IL13Rα2 was seen on all the glioma cell lines. This heterogeneity may contribute to incomplete cell killing with the individual fusion proteins and synergistic cell kill with the combination. These results suggest that both fusion proteins may yield antitumor effects in patients with recurrent gliomas and that combination fusion protein intracranial therapy of malignant gliomas may yield an improved therapeutic index.

Original languageEnglish (US)
Pages (from-to)1107-1114
Number of pages8
JournalBioconjugate Chemistry
Volume14
Issue number6
DOIs
StatePublished - Nov 2003

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Diphtheria Toxin
Exotoxins
Interleukin-13
Glioblastoma
Pseudomonas
Epidermal Growth Factor
Toxicity
Fusion reactions
Cells
Proteins
Glioma
Cell Line
Cytotoxicity
Flow cytometry
Confocal microscopy
Confocal Microscopy
Thymidine
Cell death
Cultured Cells
Flow Cytometry

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Diphtheria Toxin-Epidermal Growth Factor Fusion Protein and Pseudomonas Exotoxin-Interleukin 13 Fusion Protein Exert Synergistic Toxicity against Human Glioblastoma Multiforme Cells. / Liu, Tie Fu; Willingham, Mark C.; Tatter, Stephen B.; Cohen, Kimberley A.; Corinne Lowe, A.; Thorburn, Andrew; Frankel, Arthur E.

In: Bioconjugate Chemistry, Vol. 14, No. 6, 11.2003, p. 1107-1114.

Research output: Contribution to journalArticle

Liu, Tie Fu ; Willingham, Mark C. ; Tatter, Stephen B. ; Cohen, Kimberley A. ; Corinne Lowe, A. ; Thorburn, Andrew ; Frankel, Arthur E. / Diphtheria Toxin-Epidermal Growth Factor Fusion Protein and Pseudomonas Exotoxin-Interleukin 13 Fusion Protein Exert Synergistic Toxicity against Human Glioblastoma Multiforme Cells. In: Bioconjugate Chemistry. 2003 ; Vol. 14, No. 6. pp. 1107-1114.
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