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Title: Trastuzumab-binding peptide display by Tobacco mosaic virus

Journal Article · · Virology
; ;  [1];  [2];  [1];  [3]
  1. 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 (Russian Federation)
  2. Blokhin Cancer State Research Center, Russian Academy of Medical Sciences, Moscow (Russian Federation)
  3. Nomad Bioscience GmbH, Biozentrum Halle, Weinbergweg 22, D-06120 Halle (Saale) (Germany)

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.

OSTI ID:
21417252
Journal Information:
Virology, Vol. 407, Issue 1; Other Information: DOI: 10.1016/j.virol.2010.08.005; PII: S0042-6822(10)00522-2; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
Country of Publication:
United States
Language:
English