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Pure Appl. Chem., 2004, Vol. 76, No. 5, pp. 983-989

Passive and catalytic antibodies and drug delivery

G. M. Blackburn, J. H. Rickard, S. Cesaro-Tadic, D. Lagos, A. Mekhalfia, L. Partridge and A. Plückthun

Krebs Institute, Chemistry Department, Sheffield University, Sheffield, S3 7HF, UK; Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland; Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK

Abstract: Antibodies are one of the most promising components of the biotechnology repertoire for the purpose of drug delivery. On the one hand, they are proven agents for cell-selective delivery of highly toxic agents in a small but expanding number of cases. This technology calls for the covalent attachment of the cytotoxin to a tumor-specific antibody by a linkage that is reversible under appropriate conditions (antibody conjugate therapy, ACT —“passive delivery”). On the other hand, the linker cleavage can be accomplished by a protein catalyst attached to the tumor-specific antibody (“catalytic delivery”). Where the catalyst is an enzyme, this approach is known as antibody-directed enzyme prodrug therapy (ADEPT). Where the transformation is brought about by a catalytic antibody, it has been termed antibody-directed abzyme prodrug therapy (ADAPT). These approaches will be illustrated with emphasis on how their demand for new biotechnology is being realized by structure-based protein engineering.