Abstract
The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.
MeSH terms
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Animals
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Antibodies, Bispecific / genetics*
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Antibodies, Bispecific / immunology
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Cell Line, Tumor
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Cytokines / drug effects*
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Cytokines / immunology
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Enzyme-Linked Immunosorbent Assay
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Female
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Humans
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Immunoblotting
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Immunohistochemistry
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In Vitro Techniques
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Luminescent Measurements
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred NOD
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Neoplasms / immunology
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Neoplasms / pathology
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Neoplasms / therapy*
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RNA, Messenger / genetics
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RNA, Messenger / pharmacology*
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T-Lymphocytes / drug effects*
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Tumor Burden / drug effects*
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Bispecific
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Cytokines
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RNA, Messenger