Abstract
Several low- or non-FcR binding anti-human CD3 monoclonal antibodies have been under investigation for the treatment of autoimmune diseases. To model the mechanism of action of these anti-human CD3 mAbs in the murine system, an Fc-modified anti-mouse CD3 antibody (N297A) was generated. N297A exhibited similar biological effects as Fc-modified anti-human CD3 antibodies including rapid, reversible reduction in peripheral leukocyte numbers, differential modulation of activated versus resting T cells, and reduced levels of induced cytokine release compared to the non-Fc-modified parent antibody. In an in vivo model of colitis induced by adoptive transfer of IL-10-deficient cells, administration of N297A significantly reduced body weight loss. As N297A shared many functional characteristics of non-FcR binding anti-human CD3 mAbs both in vitro and in vivo, it provides a means to model the mechanisms of action of Fc-modified anti-human CD3 antibodies in mouse.
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / metabolism
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Apoptosis / drug effects
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CD3 Complex / immunology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology
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CHO Cells
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Colitis / immunology
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Colon / drug effects
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Colon / pathology
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Cricetinae
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Cricetulus
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Cytokines / metabolism
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Humans
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Lymphocyte Count
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Ovalbumin / immunology
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Protein Binding
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, IgG / immunology
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Receptors, IgG / metabolism*
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Recombinant Fusion Proteins / administration & dosage*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
Substances
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Antibodies, Monoclonal
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CD3 Complex
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Cytokines
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, IgG
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Recombinant Fusion Proteins
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Ovalbumin