Cell Receptor Specific Targeted Toxins: Genetic Construction and Characterization of an Interleukin 2 Diphtheria Toxin-Related Fusion Protein

J. R. Murphy Evans Department of Clinical Research and Department of Medicine, The University Hospital, Boston University Medical Center, Boston, MA, 02118

D. P. Williams Department of Microbiology, Boston University School of Medicine, Boston, MA, 02118

P. Bacha Seragen Inc., Hopkinton, MA, 01748

W. Bishai Evans Department of Clinical Research and Department of Medicine, The University Hospital, Boston University Medical Center, Boston, MA, 02118; Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, 02115

C. Waters Seragen Inc., Hopkinton, MA, 01748

T. B. Strom Charles A. Dana Resarch Institute, Harvard Thorndike Laboratory of the Beth Israel Hospital, Harvard Medical School, Boston, MA, 02215

Abstract

We have genetically replaced the diphtheria toxin receptor binding domain with a DNA insert encoding the T-cell growth factor interleukin-2 (IL-2). The toxin-related IL-2 fusion gene encodes a 70,586 dalton protein, pro-IL-2-toxin. The mature form of IL-2-toxin is exported to the periplasmic space of recombinant Escherichia coli and has a molecular weight of 68,086. IL-2-toxin has been partially purified from periplasmic extracts of recombinant E. coli, and it is shown to contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. The chimeric toxin is targeted toward IL-2 receptor bearing T-cells in vitro.

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Cell Receptor Specific Targeted Toxins: Genetic Construction and Characterization of an Interleukin 2 Diphtheria Toxin-Related Fusion Protein

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Cell Receptor Specific Targeted Toxins: Genetic Construction and Characterization of an Interleukin 2 Diphtheria Toxin-Related Fusion Protein

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