The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells

Jason G. Ramage, Daniel A. Vallera, Jennifer H. Black, Peter D. Aplan, Ursula R. Kees, Arthur E. Frankel

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant acute myelogenous leukemia (AML). We prepared diphtheria toxin/urokinase fusion protein (DTAT) composed of the amino terminal fragment of the urokinase-type plasminogen activator (uPA) fused to the catalytic and translocation domains of diphtheria toxin (DT) and assessed its activity on leukemic cell lines. The number of uPA receptors (uPAR or CD87) was measured using a phycoerythrin conjugated monoclonal antibody to CD87 and flow cytometry. Seven of 23 cell lines (30%) showed CD87 expression (≥5000 receptors/cell). DTAT cytotoxicity (IC50≤30pM) was observed in all seven of these samples and none of the 16 samples with low or absent CD87 expression. There was a significant correlation between DTAT sensitivity and CD87 density (P=0.0007). These results show that specific CD87 binding is one factor important in the sensitivity of patient's leukemic blasts to DTAT and demonstrate for the first time that the CD87/uPAR can be used as a target for fusion protein therapy of AML.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalLeukemia Research
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

Diphtheria Toxin
Poisons
Urokinase-Type Plasminogen Activator
Acute Myeloid Leukemia
Phycoerythrin
Urokinase Plasminogen Activator Receptors
Cell Line
Proteins
Diphtheria
Catalytic Domain
Flow Cytometry
Monoclonal Antibodies
Drug Therapy
Therapeutics

Keywords

  • Acute myeloid leukemia
  • Diphtheria fusion protein
  • Urokinase receptor

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells. / Ramage, Jason G.; Vallera, Daniel A.; Black, Jennifer H.; Aplan, Peter D.; Kees, Ursula R.; Frankel, Arthur E.

In: Leukemia Research, Vol. 27, No. 1, 01.01.2003, p. 79-84.

Research output: Contribution to journalArticle

Ramage, Jason G. ; Vallera, Daniel A. ; Black, Jennifer H. ; Aplan, Peter D. ; Kees, Ursula R. ; Frankel, Arthur E. / The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells. In: Leukemia Research. 2003 ; Vol. 27, No. 1. pp. 79-84.
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