ABSTRACT
Antibodies are the most rapidly growing class of human therapeutics and the second
largest class of drugs after vaccines. At present, several antibodies are approved
for therapeutic use in diverse clinical settings, including oncology, chronic inflammatory
diseases, transplantation, infectious diseases, and cardiovascular medicine. These
approved antibody therapeutics include unmodified immunoglobulin G molecules, radioimmunoconjugates,
antibody-drug conjugates, and fragment antigen-binding molecules. At least 150 additional
antibodies are in clinical development. A major strength of therapeutic antibodies
is their established properties as a drug class with high success rates from clinical
trials to regulatory approvals. Much of the experience gained from the generation
and optimization of one antibody is applicable to other antibodies. Antibody fragments
are a subclass with growing clinical importance. This review focuses on single-chain
antibodies as the smallest possible format for recombinant antibodies, and their use
as antithrombotic drugs. We describe different antibody formats, the current applications
of antibody fragments, and their generation by cloning from hybridoma cell lines as
well as their selection from antibody libraries. We review the use of antibody fragments
for thrombus targeting using fibrin and platelet-specific single-chain antibodies
in combination with anticoagulants and thrombolytic agents as antithrombotic drugs.
KEYWORDS
Antibody fragments - hybridoma - thrombosis - phage display - glycoprotein (GP) IIb-IIIa
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Karlheinz PeterM.D.
Baker Heart Research Institute
P.O. Box 6492 St Kilda Road Central, Melbourne, Victoria 8008, Australia
eMail: karlheinz.peter@baker.edu.au
