Diphtheria toxin-related cytokine fusion proteins: elongation factor 2 as a target for the treatment of neoplastic disease |
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| Authors: | Johanna vander Spek Larry Cosenza Thasia Woodworth Jean C Nichols John R Murphy |
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| Institution: | (1) Evans Department of Clinical Research and Department of Medicine, Boston University Medical Center Hospital, 02118 Boston, MA;(2) Department of Pharmacology, Boston University School of Medicine, 02118 Boston, MA;(3) Seragen Inc., 01748 Hopkinton, MA, USA |
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| Abstract: | 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. |
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| Keywords: | diphtheria toxin protein engineering interleukin-2 fusion toxin phase I/II clinical trials targeted cytotoxins |
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