Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-03-28
1998-12-29
Duffy, Patricia
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 71, 5303879, 5303881, 53038826, G01N 3353, C07K 1600
Patent
active
058540067
ABSTRACT:
An antibody is provided which binds to active GGT, and can identify tissues which express GGT on their surface. Many solid tumors express GGT on their surface. Individuals identified with such tumors may be treated with inactivated prodrugs of chemotherapeutic agents at local dosage levels substantially above the maximum dosage levels currently permitted due to side effect limitations. The prodrugs are comprised of chemotherapeutic agents rendered inactive by the attachment of a gamma-glutamyl group thereto. The gamma-glutamyl group is cleaved by GGT on the surface of solid tumor cells expressing GGT, and thus active only locally against the tumor. Side effects are suppressed. The antibody is used to identify solid tumors that are candidates for this treatment, as well as to identify tissues which express GGT and which must therefore be the basis of selection criteria of various available chemotherapeutic agents.
REFERENCES:
Hanigan et al., Immunohistochemical Detection of Gamma-Glutamyl Transpeptidase in Normal Human Tissue, J. Histochem. Cytochem. 44:1101-1108, 1996.
Shiozawa et al., A Monoclonal Antibody against Human Kidney Gamma-Glutamyl Transpeptidase: Preparation, Immunochemical, and Immunohistochemical Characterization, J. Histochem. Cytochem. 37:1053-1061, 1989.
Glass et al., Detection of Conformational Changes in rat kidney Gamma-Glutamyl Transpeptidase by an Antibody against a Synthethic Peptide Belonging to Part of the Reactive Centre of the Enzyme, Biochem. Mol. Biol. Int. 33:505-513, 1994.
Palfreyman et al., Guidelines for the Production of Polypeptide Specific Antisera Using Small Synthetic Oligopeptides as Immunogens, J. Immunological Methods 75:383-393, 1984.
Sakamuro et al., The Primary Structure of Human Gamma-Glutamyl Transpeptidase, Gene 73:1-9, 1988.
Tate et al., Renal Gamma-Glutamyl Transpeptidases: Structural and Immunological Studies, Arch. Biochem. Biophys. 262:397-408, 1988.
Hanigan Marie
MacDonald Timothy
Duffy Patricia
The University of Virginia
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