Monoclonal antibodies are increasingly being used as therapeutic agents in a wide range of indications, including oncology, inflammation and infectious disease. In most cases the basis of the therapeutic function is the high degree of specificity and affinity the antibody-based drug has for its target antigen. However, the mechanism of action (MOA), the way the drug takes advantage of this specificity to mediate a therapeutic effect, varies considerably from drug to drug. Three basic potential categories of MOAs exist: antagonists, agonists and specific delivery mechanisms to target an active function to a particular cell type. The latter functions include selective cell killing, based on Fc-mediated events, recruitment of effector cells, and drug or radioisotope delivery. The majority of these mechanisms are not necessarily optimally mediated by an IgG structure; clearly, in the case of antibody-dependent cellular cytotoxicity or complement-mediated lysis, Fc is required. However, Fab fragments (the fragment comprising one antigen-binding arm of the Y-shaped IgG molecule) can be formatted to mediate most mechanisms and have the advantage that valency and half-life can be controlled to simplify the drug and address only the mechanism required. Moreover, Fab fragments can be produced in microbial expression systems which address manufacturing issues such as scale of supply and cost of goods.
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August 2002
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Conference Article|
August 01 2002
Formatting antibody fragments to mediate specific therapeutic functions
A. N. C. Weir;
A. N. C. Weir
1
1Celltech R+D Ltd., 216 Bath Road, Slough, Berkshire SLI 4EN, U.K.
1To whom correspondence should be addressed (e-mail neil.weir@slh.celltechgroup.com)
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A. Nesbitt;
A. Nesbitt
1Celltech R+D Ltd., 216 Bath Road, Slough, Berkshire SLI 4EN, U.K.
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A. P. Chapman;
A. P. Chapman
1Celltech R+D Ltd., 216 Bath Road, Slough, Berkshire SLI 4EN, U.K.
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A. G. Popplewell P. Antoniw;
A. G. Popplewell P. Antoniw
1Celltech R+D Ltd., 216 Bath Road, Slough, Berkshire SLI 4EN, U.K.
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A. D. G. Lawson
A. D. G. Lawson
1Celltech R+D Ltd., 216 Bath Road, Slough, Berkshire SLI 4EN, U.K.
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Publisher: Portland Press Ltd
Received:
March 11 2002
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (4): 512–516.
Article history
Received:
March 11 2002
Citation
A. N. C. Weir, A. Nesbitt, A. P. Chapman, A. G. Popplewell P. Antoniw, A. D. G. Lawson; Formatting antibody fragments to mediate specific therapeutic functions. Biochem Soc Trans 1 August 2002; 30 (4): 512–516. doi: https://doi.org/10.1042/bst0300512
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