DAB389EGF fusion protein therapy of refractory glioblastoma multiforme

Kimberley A. Cohen, TieFu Liu, Reid Bissonette, Raj K. Puri, Arthur E. Frankel

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Primary brain tumors including anaplastic astrocytomas and glioblastoma multiforme are difficult to treat because of their locally invasive nature and chemoradioresistance. Novel therapies are needed. One class of therapeutics is fusion proteins consisting of peptide toxins fused to brain tumor selective ligands. DAB389EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). DAB389EGF is selectively toxic to EGF receptor (EGFR) overexpressing cells. Close to half of all high-grade primary brain tumors have EGFR gene amplification and EGFR overexpression. With the use of convection-enhanced delivery (CED), DAB389EGF may be delivered locally at high concentrations to the brain tumor. CED would avoid many of the pharmacologic and toxicologic barriers which have limited effective use of this agent including rapid clearance from the circulation, high anti-diphtheria toxin antibody titers in the blood and toxicities to the liver and kidney. Both cell lines and animal models are available to assess the potential of this agent for brain tumor therapy. Since significant amounts of clinical grade DAB389EGF are available, some careful additional preclinical efficacy work should lead to testing of this agent in patients within the next few years.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalCurrent Pharmaceutical Biotechnology
Volume4
Issue number1
DOIs
StatePublished - Feb 2003

Fingerprint

Glioblastoma
Brain Neoplasms
Epidermal Growth Factor Receptor
Diphtheria Toxin
Convection
Proteins
histidinoalanine
Therapeutics
Gene Amplification
Poisons
Astrocytoma
Proxy
Epidermal Growth Factor
Catalytic Domain
Animal Models
Ligands
Kidney
Cell Line
Peptides
Antibodies

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Biotechnology

Cite this

DAB389EGF fusion protein therapy of refractory glioblastoma multiforme. / Cohen, Kimberley A.; Liu, TieFu; Bissonette, Reid; Puri, Raj K.; Frankel, Arthur E.

In: Current Pharmaceutical Biotechnology, Vol. 4, No. 1, 02.2003, p. 39-49.

Research output: Contribution to journalArticle

Cohen, Kimberley A. ; Liu, TieFu ; Bissonette, Reid ; Puri, Raj K. ; Frankel, Arthur E. / DAB389EGF fusion protein therapy of refractory glioblastoma multiforme. In: Current Pharmaceutical Biotechnology. 2003 ; Vol. 4, No. 1. pp. 39-49.
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