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Identification of FGF receptor-binding peptides for cancer gene therapy

By F. Maruta, A. Parker, K.D. Fisher, M.T. Hallissey, T. Ismail, D.C. Rowlands, L.A. Chandler, D.J. Kerr and L.W. Seymour

Abstract

In this paper we describe how small (7-mer) oligopeptides were iterated using phage display technology that bind to bFGF receptors. The receptors for bFGF have been shown to be upregulated in numerous tumours in vivo, presumably to help stimulate angiogensis. Therefore, the possibility of using bFGF to target gene delivery vectors (or chemotherapeutic drugs) to the the tumour vasculature is an appealing one. However, the likelihood of being able to use bFGF systemically is limited by the large, hydrophobic nature of the molecule, its difficulty (and cost) to mass produce, its potential angiogenic effects, and potential interaction with the bodies natural vasculature, presumably lowering the dose limiting toxicity. Therefore, we reasoned that small, oligopeptides that bind to the same receptor (both on cells in vitro, and resected tumours ex vivo), could easily be incorporated into either viral, or non-viral gene delivery vectors mediating selective delvery of their DNA payload to the bFGF recptor expressing cells of the tumour vasculature. Importantly, whilst the peptides were shown to bind to bFGF receptors, they did not stimulate the strong mitogenic effect observed using bFG

Publisher: NewsRx
Year: 2002
OAI identifier: oai:eprints.gla.ac.uk:57731
Provided by: Enlighten
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