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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Vydáno v:	Nature medicine Ročník 23; číslo 7; s. 815 - 817
Hlavní autoři:	Stadler, Christiane R, Bähr-Mahmud, Hayat, Celik, Leyla, Hebich, Bernhard, Roth, Alexandra S, Roth, René P, Karikó, Katalin, Türeci, Özlem, Sahin, Ugur
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.07.2017 Nature Publishing Group
Témata:	13/1 13/109 13/31 13/51 38/1 42/109 631/61/51/1568 692/699/67/580 692/700/565/1436/152 82/1 82/29 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
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/nm.4356