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,
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 tech-
nology 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.
*Lecture presented at the Polish-Austrian-German-Hungarian-Italian Joint Meeting on Medicinal Chemistry, Kraków, Poland, 15-18 October 2003. Other presentations are published in this issue, pp. 907 -1032.
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