Diphtheria toxin-related cytokine fusion proteins: elongation factor 2 as a target for the treatment of neoplastic disease.
We have used protein engineering and recombinant DNA methodologies in order to construct a fusion protein in which human interleukin-2 (IL-2) is genetically linked to the catalytic and transmembrane domains of diphtheria toxin. The fusion toxin, DAB486IL-2, is highly cytotoxic for only those cells which display the high affinity interleukin-2 receptor (IL-2R) on their surface. In phase I/II clinical studies the intravenous administration of DAB486IL-2 has been found to be safe, well tolerated and may lead to the induction of durable remissions in patients presenting with a variety of IL-2R positive lymphomas.
vanderSpek
J
J
Evans Department of Clinical Research, Boston University Medical Center Hospital, MA 02118.
Cosenza
L
L
Woodworth
T
T
Nichols
J C
JC
Murphy
J R
JR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002384:Catalysis; D004167:Diphtheria Toxin / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000187:drug effects*; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D011993:Recombinant Fusion Proteins