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Antigen binding and biological activities of engineered mutant chimeric antibodies with human tumor specificities

Antigen binding and biological activities of engineered mutant chimeric antibodies with human... The constant region of the human γ1 chain was mutated either by deleting the second domain (CH2) or by mutating the two hinge region cysteine residues, normally involved in the inter-heavy chain disulfide bondformation, to serines. The effects of these mutations on chain assembly, antigen binding, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC) were measured after expressing the human constant regions together with mouse variable regions encoding anti-tumor cell specificities. The CH2-deleted chimeric antibody was found to have increased antigen binding activity and little (ADCC) or no (CDC) biological activity. The cysteine to serine hinge region mutant antibody had normal or slightly reduced antigen binding activity, greatly reduced ADCC. activity, and a reduced, but still significant, ability to mediate CDC. These results reflect the complexity of the interactions between the immunoglobulin domains and their role in balancing the antigen binding and effector functions of antibodies. They suggest further that such antibodies may be useful in applications, such as the in vivo imaging of tumors, where the loss of effector function (e.g., Fe receptor binding) is desired. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Antibodies IOS Press

Antigen binding and biological activities of engineered mutant chimeric antibodies with human tumor specificities

Human Antibodies , Volume 1 (1) – Jan 1, 1990

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References (2)

Publisher
IOS Press
Copyright
Copyright © 1990 by IOS Press, Inc
ISSN
1093-2607
eISSN
1875-869X
DOI
10.3233/HAB-1990-1109
Publisher site
See Article on Publisher Site

Abstract

The constant region of the human γ1 chain was mutated either by deleting the second domain (CH2) or by mutating the two hinge region cysteine residues, normally involved in the inter-heavy chain disulfide bondformation, to serines. The effects of these mutations on chain assembly, antigen binding, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC) were measured after expressing the human constant regions together with mouse variable regions encoding anti-tumor cell specificities. The CH2-deleted chimeric antibody was found to have increased antigen binding activity and little (ADCC) or no (CDC) biological activity. The cysteine to serine hinge region mutant antibody had normal or slightly reduced antigen binding activity, greatly reduced ADCC. activity, and a reduced, but still significant, ability to mediate CDC. These results reflect the complexity of the interactions between the immunoglobulin domains and their role in balancing the antigen binding and effector functions of antibodies. They suggest further that such antibodies may be useful in applications, such as the in vivo imaging of tumors, where the loss of effector function (e.g., Fe receptor binding) is desired.

Journal

Human AntibodiesIOS Press

Published: Jan 1, 1990

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