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Differences in promiscuity for antibody-FcRn interactions across species: Implications for therapeutic antibodies

Differences in promiscuity for antibody-FcRn interactions across species: Implications for therapeutic antibodies
Differences in promiscuity for antibody-FcRn interactions across species: Implications for therapeutic antibodies

Preclinical tests of therapeutic antibodies are frequently carried out in mice to evaluate pharmacokinetics and efficacy. However, the observation that mouse IgG are cleared rapidly from the human circulation suggests that mice may not always be an ideal model. The Fc receptor, FcRn, regulates the serum half-lives of IgG in mice and most likely has a similar function in humans. In the current study we have carried out an extensive analysis of the interaction of the human or mouse forms of FcRn with IgG from various species using surface plasmon resonance. We show that in contrast to mouse FcRn, human FcRn is surprisingly stringent in its binding specificity for IgG derived from different species. Human FcRn binds to human, rabbit and guinea pig IgG, but not significantly to rat, bovine, sheep or mouse IgG (with the exception of weak binding to mouse IgG2b). In contrast, mouse FcRn binds to all IgG analyzed. The lack of binding of human FcRn to mouse IgG1 has been confirmed using transfectants that have been engineered to express human FcRn on the cell surface. Our results provide a molecular explanation for the enigmatic observation that mouse IgG behave anomalously in humans. These studies have implications for the successful application of therapeutic antibodies.

Antibody, FcRn, Interactions, Promiscuity, Therapeutic antibodies
0953-8178
1551-1559
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Radu, Caius G.
7b0cdea8-4ad8-4c89-89f7-eb6083504c1c
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Radu, Caius G.
7b0cdea8-4ad8-4c89-89f7-eb6083504c1c
Ghetie, Victor
b7b50946-2bd9-4896-b841-6bbfba8237c2
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Ober, Raimund J., Radu, Caius G., Ghetie, Victor and Ward, E. Sally (2001) Differences in promiscuity for antibody-FcRn interactions across species: Implications for therapeutic antibodies. International Immunology, 13 (12), 1551-1559. (doi:10.1093/intimm/13.12.1551).

Record type: Article

Abstract

Preclinical tests of therapeutic antibodies are frequently carried out in mice to evaluate pharmacokinetics and efficacy. However, the observation that mouse IgG are cleared rapidly from the human circulation suggests that mice may not always be an ideal model. The Fc receptor, FcRn, regulates the serum half-lives of IgG in mice and most likely has a similar function in humans. In the current study we have carried out an extensive analysis of the interaction of the human or mouse forms of FcRn with IgG from various species using surface plasmon resonance. We show that in contrast to mouse FcRn, human FcRn is surprisingly stringent in its binding specificity for IgG derived from different species. Human FcRn binds to human, rabbit and guinea pig IgG, but not significantly to rat, bovine, sheep or mouse IgG (with the exception of weak binding to mouse IgG2b). In contrast, mouse FcRn binds to all IgG analyzed. The lack of binding of human FcRn to mouse IgG1 has been confirmed using transfectants that have been engineered to express human FcRn on the cell surface. Our results provide a molecular explanation for the enigmatic observation that mouse IgG behave anomalously in humans. These studies have implications for the successful application of therapeutic antibodies.

Full text not available from this repository.

More information

Accepted/In Press date: 12 September 2001
Published date: 1 December 2001
Keywords: Antibody, FcRn, Interactions, Promiscuity, Therapeutic antibodies

Identifiers

Local EPrints ID: 424919
URI: http://eprints.soton.ac.uk/id/eprint/424919
ISSN: 0953-8178
PURE UUID: b1299003-986f-40d0-99ca-d836e6d9f522
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 05 Oct 2018 16:30
Last modified: 07 Oct 2020 02:22

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Contributors

Author: Raimund J. Ober ORCID iD
Author: Caius G. Radu
Author: Victor Ghetie
Author: E. Sally Ward ORCID iD

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