Diphtheria toxin-based receptor-specific chimaeric toxins as targeted therapies.

Abstract

The results from the phase I/II studies of the intravenous administration of DAB486-IL-2 to patients with refractory haematological malignancies have now proven in principle the feasibility of fusion toxin therapy in man. Indeed, the cell-surface receptor-specific intoxication of neoplastic cells through the catalytic ADP-ribosylation of EF-2 is the prototype of a new class of biological response modifiers that may be generally applicable. In those circumstances where either the de novo expression or up-regulation of a cell-surface receptor can be associated with human disease [e.g. the up-regulation of the epidermal growth factor (EGF) receptor on breast cancer], it should be possible to construct genetically a DT-related/growth factor fusion protein to produce an experimental biological treatment of that malignancy. The EGF receptor-targeted fusion toxin DAB389-EGF has within the last year begun human phase I clinical trials. The pre-clinical development of DAB389-IL-7 has begun with the anticipation that this novel fusion toxin will be evaluated in the treatment of the acute leukaemias in which the IL-7R has been shown to be present.

• Authors: E B Sweeney, J R Murphy
• Journal: Essays in biochemistry (Essays Biochem) Vol. 30 Pg. 119-31 ( 1995) ISSN: 0071-1365 [Print] England
• PMID: 8822152 (Publication Type: Journal Article, Review)

Chemical References

• Antigens, CD
• Diphtheria Toxin
• Immunotoxins
• Receptors, Interleukin
• Receptors, Interleukin-7
• Recombinant Fusion Proteins

Topics

• Amino Acid Sequence
• Animals
• Antigens, CD (metabolism)
• Cell Line
• Diphtheria Toxin (metabolism)
• Genetic Engineering
• Humans
• Immunotoxins (metabolism)
• Molecular Sequence Data
• Molecular Structure
• Multigene Family
• Receptors, Interleukin (metabolism)
• Receptors, Interleukin-7
• Recombinant Fusion Proteins (metabolism)