Abstract
Antibodies are currently the fastest growing class of therapeutic proteins. When antibody fragments are included, there are over thirty-five antibody-based medicines approved for human therapy. Many more antibody and antibody-like fragments are being evaluated clinically. Production of antibody fragments can be efficient and their compact size can allows for better tissue extravasation into solid tumors than full antibodies. Unfortunately, a key limitation of antibody fragments for systemic use is their short half-life in circulation. Prolonging their circulation half-life can be accomplished clinically by the covalent conjugation of the antibody fragment to the water-soluble polymer, poly(ethylene glycol) (PEG). Many polymers and strategies are also being pursued to increase antibody fragment half-life.
Highlights
Kohler and Milstein in 1975 described how antibodies could be made by fusing murine B lymphocytes with myeloma cells to generate hybrid cells
Their in vivo findings found a moderate increase in half-life from 6 h to 2 h with the 200 residue HAPylated Fab fragment compared to the Fab fragment alone [82]
This review summarises the strategies used to increase the half-life of therapeutic antibody fragments and the use of antibody fragments to extend the half-life of other molecules
Summary
Kohler and Milstein in 1975 described how antibodies could be made by fusing murine B lymphocytes with myeloma cells to generate hybrid cells (hybridomas). When considering production as a limiting factor, solutions have included the production of antibody fragments such as Fab, Fv and scFv using microbial expression systems. These systems can provide greater amounts of the desired protein compared to earlier eukaryotic systems [13]. One advantage is that antibody fragments due to their smaller size can penetrate tissue more rapidly than full IgG molecules. This property has been exploited to develop diagnostics, with three in vivo imaging.
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