Diphtheria toxin-based receptor-specific chimaeric toxins as targeted therapies.
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.
Sweeney
E B
EB
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA.
Murphy
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D004167:Diphtheria Toxin / Q000378:metabolism*; D005818:Genetic Engineering; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D018123:Receptors, Interleukin / Q000378:metabolism*; D020395:Receptors, Interleukin-7; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D015703:Antigens, CD; D004167:Diphtheria Toxin; D000922:Immunotoxins; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D011993:Recombinant Fusion Proteins