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15 - Alternative Antibody Formats

from PART VI - NOVEL ANTIBODY FORMATS

Published online by Cambridge University Press:  15 December 2009

By
Fabrice Le Gall  and
Melvyn Little
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

During evolution, antibodies have acquired several invaluable properties that are now being exploited for clinical applications. First, they can bind a wide variety of target molecules with exquisite specificity. This property can be used to block the action of ligands such as TNFα in patients with rheumatoid arthritis or the Her-2 receptor in patients with breast cancer. In contrast to this mode of action, antibodies can also imitate ligand binding and stimulate various signaling pathways. Antibodies binding to CD20, for example, can induce apoptotic signals in the malignant cells of patients with non-Hodgkin's lymphoma. Additional effector functions are provided by the Fc domains, which can induce cell lysis by binding to complement (CDC) or by binding to Fc receptors on natural killer cells and macrophages (ADCC). An additional binding domain for the neonatal receptor on endothelial cells facilitates their uptake and recycling, enabling antibody therapeutics to remain in the circulation for many weeks.

To optimize the properties of an antibody for a particular indication or for use as a diagnostic, it would be preferable to improve or even delete particular characteristics. For example, to achieve better tumor penetration or a better tumor-to-blood ratio for visualizing metastases, it would be preferable to have a relatively small antibody fragment with a fairly short half-life. On the other hand, the antibody should not be too small in order to avoid a rapid clearance immediately after its application. It would also be very advantageous for certain clinical applications to improve the effector functions.

Type
Chapter
Information
Recombinant Antibodies for Immunotherapy , pp. 203 - 215
Publisher: Cambridge University Press
Print publication year: 2009

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