Trastuzumab-binding peptide display by Tobacco mosaic virus

Abstract Human epidermal growth factor receptor-2 (HER2/neu) is a target for the humanized monoclonal antibody trastuzumab. Recently, trastuzumab-binding peptides (TBP) of HER2/neu that inhibit proliferation of breast cancer cells were identified. We have now studied conditions of efficient assembly...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2010-11, Vol.407 (1), p.7-13
Main Authors: Frolova, Olga Y, Petrunia, Igor V, Komarova, Tatiana V, Kosorukov, Vyacheslav S, Sheval, Eugene V, Gleba, Yuri Y, Dorokhov, Yuri L
Format: Article
Language:English
Subjects:
ANTIBODIES
Antibodies, Monoclonal - metabolism
Antibodies, Monoclonal, Humanized
BODY
Capsid Proteins - genetics
Capsid Proteins - metabolism
DISEASES
Genetic Vectors
GLANDS
GROWTH FACTORS
HER2/neu
Humans
Infectious Disease
MAMMARY GLANDS
MEMBRANE PROTEINS
MICROORGANISMS
MITOGENS
MONOCLONAL ANTIBODIES
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PARASITES
Peptide display
PEPTIDES
Peptides - genetics
Peptides - metabolism
Potato virus X
Protein Binding
PROTEINS
RADIOLOGY AND NUCLEAR MEDICINE
RECEPTORS
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Rhizobium - genetics
TOBACCO MOSAIC VIRUS
Tobacco Mosaic Virus - genetics
Tobacco Mosaic Virus - metabolism
Trastuzumab
Virus assembly
VIRUSES
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Summary:Abstract Human epidermal growth factor receptor-2 (HER2/neu) is a target for the humanized monoclonal antibody trastuzumab. Recently, trastuzumab-binding peptides (TBP) of HER2/neu that inhibit proliferation of breast cancer cells were identified. We have now studied conditions of efficient assembly in vivo of Tobacco mosaic virus (TMV)-based particles displaying TBP on its surface. The system is based on an Agrobacterium -mediated co-delivery of binary vectors encoding TMV RNA and coat protein (CP) with TBP in its C-terminal extension into plant leaves. We show how the fusion of amino acid substituted TBP (sTBP) to CP via a flexible peptide linker can improve the manufacturability of recombinant TMV (rTMV). We also reveal that rTMV particles with exposed sTBP retained trastuzumab-binding capacity but lost an anti-HER2/neu immunogenic scaffold function. Mouse antibodies against rTMV did not recognize HER2/neu on surface of human SK-BR-3 cells.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2010.08.005