Abstract
Phagocytosis plays important roles both in homeostasis and under pathological conditions. Fcγ receptor-mediated phagocytosis has been exploited as an integral mechanism for antibody-based therapies. Unlike Fcγ receptor-mediated phagocytosis, MerTK-mediated phagocytic clearance is immunologically silent. Here, we describe a bispecific antibody approach to harness MerTK for targeted clearance without inducing proinflammatory cytokine release associated with Fcγ receptor engagement. We generated bispecific antibodies targeting live B cells or amyloid beta aggregates to demonstrate the feasibility and versatility of this new approach.
Keywords:
Fcγ receptor; MerTK; Phagocytosis; bispecific antibody; immunologically silent.
MeSH terms
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Amyloid beta-Peptides / immunology*
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Animals
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Antibodies, Bispecific / genetics
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Antibodies, Bispecific / metabolism*
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Antigens, CD20 / immunology
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Antigens, CD20 / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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Cells, Cultured
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Cytokines / metabolism
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Humans
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Immune Tolerance
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Inflammation Mediators / metabolism
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Macrophages / immunology
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Macrophages / metabolism*
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Mice
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Mice, Knockout
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Microglia / metabolism*
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Molecular Targeted Therapy
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Phagocytosis
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Receptors, IgG / metabolism
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c-Mer Tyrosine Kinase / agonists*
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c-Mer Tyrosine Kinase / genetics
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c-Mer Tyrosine Kinase / immunology
Substances
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Amyloid beta-Peptides
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Antibodies, Bispecific
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Antigens, CD20
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Cytokines
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Inflammation Mediators
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Receptors, IgG
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c-Mer Tyrosine Kinase