Trastuzumab-binding peptide display by Tobacco mosaic virus.
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.
Frolova
Olga Y
OY
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University and N.I. Vavilov Institute of General Genetics, Russian Academy of Science, Moscow 119992, Russia.
Petrunia
Igor V
IV
Komarova
Tatiana V
TV
Kosorukov
Vyacheslav S
VS
Sheval
Eugene V
EV
Gleba
Yuri Y
YY
Dorokhov
Yuri L
YL
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D061067:Antibodies, Monoclonal, Humanized; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012231:Rhizobium / Q000235:genetics; D014027:Tobacco Mosaic Virus / Q000235:genetics* / Q000378:metabolism*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D036022:Capsid Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D000068878:Trastuzumab