Elimination of large tumors in mice by mRNA-encoded bispecific antibodies

Bispecific antibodies that connect T cells with tumor cells can be delivered in the form of in vitro –transcribed pharmacologically optimized mRNA; when injected into mice, these mRNA-encoded antibodies reject large established tumors as efficiently as the corresponding recombinant antibody protein....

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Bibliographic Details
Published in:Nature medicine Vol. 23; no. 7; pp. 815 - 817
Main Authors: Stadler, Christiane R, Bähr-Mahmud, Hayat, Celik, Leyla, Hebich, Bernhard, Roth, Alexandra S, Roth, René P, Karikó, Katalin, Türeci, Özlem, Sahin, Ugur
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.07.2017
Nature Publishing Group
Subjects:
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13/109
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Animals
Antibodies
Antibodies, Bispecific - genetics
Antibodies, Bispecific - immunology
Biomedicine
Bispecific antibodies
brief-communication
Cancer Research
Cell Line, Tumor
Cells
Coding
Cytokines
Cytokines - drug effects
Cytokines - immunology
Cytotoxicity
Dosage and administration
Drug dosages
Drug therapy
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunoblotting
Immunoglobulins
Immunohistochemistry
In vitro methods and tests
In Vitro Techniques
Infectious Diseases
Luminescent Measurements
Lymphocytes
Lymphocytes T
Male
Manufacturing
Medical research
Messenger RNA
Metabolic Diseases
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Molecular Medicine
Monoclonal antibodies
mRNA
Neoplasms - immunology
Neoplasms - pathology
Neoplasms - therapy
Neurosciences
Ovaries
Pharmacology
Plasma
Proteins
Ribonucleic acid
RNA
RNA, Messenger - genetics
RNA, Messenger - pharmacology
T cell receptors
T cells
T-Lymphocytes - drug effects
Tumor Burden - drug effects
Tumor cells
Tumors
Xenograft Model Antitumor Assays
ISSN:1078-8956, 1546-170X, 1546-170X
Online Access:Get full text
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Description
Summary:Bispecific antibodies that connect T cells with tumor cells can be delivered in the form of in vitro –transcribed pharmacologically optimized mRNA; when injected into mice, these mRNA-encoded antibodies reject large established tumors as efficiently as the corresponding recombinant antibody protein. 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.
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ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/nm.4356