Pseudomonas exotoxin conjugate immunotoxins

Drug – bio-affecting and body treating compositions – Lymphokine

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424 88, 424 92, 514 2, 514 6, 260112B, 260112R, A61K 3900, A61K 3902, A61K 3700, A23J 106

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045459851

ABSTRACT:
A method of modifying Pseudomonas exotoxin (PE) with methyl-4-mercaptobutyrimidate is disclosed so that after conjugating the exotoxin to a monoclonal antibody (ab) such as the antibody to the transferrin receptor, the PE-ab conjugate becomes a highly potent immunotoxin suitable for use against human tumor cells. This same method has been used to conjugate PE to epidermal growth factor (EGF) to create a highly potent growth factor-toxin conjugate for use against cells having large numbers of EGF receptors. Also disclosed are the immunotoxin conjugates for Pseudomonas exotoxin coupled to anti-TFR (antibody to the transferrin receptor) and anti-TAC (antibody to the human T-cell growth factor receptor) and to EGF.

REFERENCES:
patent: 4407965 (1983-10-01), Yamaihara
patent: 4414148 (1983-11-01), Jansen et al.
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Schreiber, Barbara Mildred, Diss. Abst., vol. 41, No. 12, Jun. 1981, p. 1405b, "In Vitro Toxicity of Antibody Pseudomona, avergihusu Exotoxin A Conjugates".
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Trowbridge et al., Nature, vol. 294, No. 12, Nov. 1981, pp. 171-173, Anti-Transferrin Receptor Monoclonal Antibody and Toxin-Antibody Conjugates Effect Growth of Human Tumor Cells".
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Terovanne et al., J. Immunological Methods, vol. 35, 1980, pp. 267-275, "Coupling of 5,3-Ketosteroid Isumerase to Human Placental Lactugen with Intramolecular Disulfide Bond Formation, Use of this Conjugate For a Sensitive Enzyme Immunoassay.
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