The binding sites on human IgG1 for human Fcγ receptor (FcγR) I, FcγRIIa, FcγRIIb, FcγRIIIa and neonatal FcR have been mapped. A common set of IgG1 residues is involved in binding to all FcγRs, while FcγRII and FcγRIII utilize distinct sites outside this common set. In addition to residues which abrogated binding to the FcγR, several positions were found which improved binding only to specific FcγRs or simultaneously improved binding to one type of FcγR and reduced binding to another type. Selected IgG1 variants with improved binding to FcγRIIIa were then tested in an in vitro antibody-dependent cellular cytotoxicity (ADCC) assay and showed an enhancement in ADCC when either peripheral blood mononuclear cells or natural killer cells were used.
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Conference Article|
August 01 2002
Engineering therapeutic antibodies for improved function
L. G. Presta;
L. G. Presta
1
1Genentech, Inc., South San Francisco, CA 94080, U.S.A.
1To whom correspondence should be addressed, at DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, U.S.A. (e-mail: leonard.presta@dnax.org)
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R. L. Shields;
R. L. Shields
1Genentech, Inc., South San Francisco, CA 94080, U.S.A.
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A. K. Namenuk;
A. K. Namenuk
1Genentech, Inc., South San Francisco, CA 94080, U.S.A.
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K. Hong;
K. Hong
1Genentech, Inc., South San Francisco, CA 94080, U.S.A.
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Y. G. Meng
Y. G. Meng
1Genentech, Inc., South San Francisco, CA 94080, U.S.A.
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Publisher: Portland Press Ltd
Received:
March 14 2002
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (4): 487–490.
Article history
Received:
March 14 2002
Citation
L. G. Presta, R. L. Shields, A. K. Namenuk, K. Hong, Y. G. Meng; Engineering therapeutic antibodies for improved function. Biochem Soc Trans 1 August 2002; 30 (4): 487–490. doi: https://doi.org/10.1042/bst0300487
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