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Session 10: Applied technologies - II

Session 10: Applied technologies - II The potentials for the use of drug-specific antibodies or Fab fragments to detoxify patients suffering from overdoses occurring during therapeutic treatment or from the self-administration of drugs of abuse have long been recognized. However, the inherent difficulties resulting from the use of foreign-species proteins such as sheep polyclonal antibodies (Abs) or mouse monoclonal antibodies (mAbs) have restricted their use. Immunization of transgenic mice with “humanized” humoral systems [1,2] with hapten-carrier conjugates has allowed us to generate hybridoma cell lines that secrete human sequence mAbs of high affinity and specificity against the low molecular weight drugs digoxin and cocaine [3,4]. Determination of the fine-binding specificities of these mAbs has enabled us to develop 3-dimensional molecular models of their mechanisms of drug-mAb binding. These models have the potential to direct the modification of these mAbs to achieve improved affinities or broadened specificities as needed for a better clinical product. Introduction: The use of current technologies that enable the generation of human sequence mAbs from transgenic or human PBL-engrafted mice, Ab or Fab phage display and ScFv libraries rather than foreign species-derived polyclonal Abs is greatly facilitating the development of new immunological treatments. But, the clinical use of anti-drug Abs also http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Antibodies IOS Press

Session 10: Applied technologies - II

Human Antibodies , Volume 12 (1) – Jan 1, 2003
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Publisher
IOS Press
Copyright
Copyright © 2003 by IOS Press, Inc
ISSN
1093-2607
eISSN
1875-869X
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Abstract

The potentials for the use of drug-specific antibodies or Fab fragments to detoxify patients suffering from overdoses occurring during therapeutic treatment or from the self-administration of drugs of abuse have long been recognized. However, the inherent difficulties resulting from the use of foreign-species proteins such as sheep polyclonal antibodies (Abs) or mouse monoclonal antibodies (mAbs) have restricted their use. Immunization of transgenic mice with “humanized” humoral systems [1,2] with hapten-carrier conjugates has allowed us to generate hybridoma cell lines that secrete human sequence mAbs of high affinity and specificity against the low molecular weight drugs digoxin and cocaine [3,4]. Determination of the fine-binding specificities of these mAbs has enabled us to develop 3-dimensional molecular models of their mechanisms of drug-mAb binding. These models have the potential to direct the modification of these mAbs to achieve improved affinities or broadened specificities as needed for a better clinical product. Introduction: The use of current technologies that enable the generation of human sequence mAbs from transgenic or human PBL-engrafted mice, Ab or Fab phage display and ScFv libraries rather than foreign species-derived polyclonal Abs is greatly facilitating the development of new immunological treatments. But, the clinical use of anti-drug Abs also

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Human Antibodies – IOS Press

Published: Jan 1, 2003

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