Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies.

Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Research Abstract Details 

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Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Abstract Text:

Carlos Vaccaro,Roger Bawdon,Sylvia Wanjie,Raimund J Ober,E Sally Ward,

The MHC class I-related receptor, neonatal Fc receptor (FcRn), plays a central role in regulating the transport and in vivo persistence of immunoglobulin G (IgG). IgG-FcRn interactions can be targeted for engineering to modulate the in vivo longevity and transport of an antibody, and this has implications for the successful application of therapeutic IgGs. Although mice are widely used to preclinically test antibodies, human and mouse FcRn have significant differences in binding specificity. Here we show that an engineered human IgG1 has disparate properties in murine and human systems. The mutant shows improved transport relative to wild-type human IgG1 in assays of human FcRn function but has short in vivo persistence and competitively inhibits FcRn activity in mice. These studies indicate potential limitations of using mice as preclinical models for the analysis of engineered antibodies. Alternative assays are proposed that serve as indicators of the properties of IgGs in humans.

Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Publishing Authors By Initials

C Vaccaro,R Bawdon,S Wanjie,RJ Ober,ES Ward,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, fc research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, fc research

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Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 18709-14

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 20

MONTH: 11

YEAR: 2006

Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Keywords Mesh Terms:

KEYWORDS: Receptors, Fc

MESH TERMS: metabolism

Chemical & Substance for Abstract: Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Information

Substance Name: Receptors, Fc

Registry Number: 0

Grant and Affiliation Information for Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies.

AFFILIATION: Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI 55556

ACRONYM: AI

MEDLINETA: Proc Natl Acad Sci U S A

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