Abstract
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody. The Her2(Per)-S-Fab can be expressed and purified efficiently from Escherichia coli. In vitro and in vivo experiments showed Her2(Per)-S-Fab had potent cytotoxicity against Her2-positive tumor cells. Thus, Her2(Per)-S-Fab may provide an alternative to treat Her2-positive cancer patients.
MeSH terms
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Animals
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Antibodies, Bispecific / genetics*
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Antibodies, Bispecific / therapeutic use
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Antibodies, Monoclonal, Humanized / genetics
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Antibodies, Monoclonal, Humanized / therapeutic use*
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Antibody-Dependent Cell Cytotoxicity
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Breast Neoplasms / immunology
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Breast Neoplasms / therapy*
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Escherichia coli / genetics
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Immunotherapy / methods*
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MCF-7 Cells
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Mice
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Mice, SCID
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Molecular Targeted Therapy
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Neoplasm Metastasis
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Protein Engineering
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Receptor, ErbB-2 / genetics*
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Receptor, ErbB-2 / immunology
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Receptor, ErbB-2 / metabolism
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Receptors, IgG / immunology
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Signal Transduction
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Single-Domain Antibodies / genetics
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Single-Domain Antibodies / therapeutic use
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Trastuzumab / therapeutic use
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Tumor Burden
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Bispecific
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Antibodies, Monoclonal, Humanized
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Receptors, IgG
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Single-Domain Antibodies
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ERBB2 protein, human
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Receptor, ErbB-2
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pertuzumab
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Trastuzumab