Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth.

TitleDevelopment of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth.
Publication TypeJournal Article
Year of Publication2013
AuthorsBehdani, M., S. Zeinali, M. Karimipour, H. Khanahmad, S. Schoonooghe, A. Aslemarz, N. Seyed, R. Moazami-Godarzi, F. Baniahmad, M. Habibi-Anbouhi, G. Hassanzadeh-Ghassabeh, and S. Muyldermans
JournalN Biotechnol
Volume30
Issue2
Pagination205-9
Date Published2013 Jan 25
ISSN1876-4347
KeywordsADP Ribose Transferases, Bacterial Toxins, Cell Proliferation, Chromatography, Gel, Enzyme-Linked Immunosorbent Assay, Exotoxins, HEK293 Cells, Humans, Immunotoxins, Neoplasms, Recombinant Proteins, Single-Domain Antibodies, Vascular Endothelial Growth Factor Receptor-2, Virulence Factors
Abstract

Angiogenesis targeting is an attractive approach for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) is such an important target that is overexpressed in tumor vasculature compared to the endothelium cells of resting blood vessels and blocking of its signaling inhibits neovascularization and tumor metastasis. Immunotoxins represent a promising group of targeted therapeutics to combat tumors. They consist of an antibody linked to a toxin and are designed to kill specifically the tumor cells. In this study, we fused a VEGFR2-specific Nanobody, the antigen-binding single-domain fragment derived from functional Heavy-chain antibody of Camelidae, to the truncated form of Pseudomonas exotoxin A and evaluated its ability to bind the VEGFR2 molecule on the cell surface. We demonstrate that this immunotoxin inhibits the proliferation of VEGFR2-expressing cells in vitro. This finding is considered to be a significant achievement in tumor therapy and it forms a basis for further studies in animal models.

DOI10.1016/j.nbt.2012.09.002
Alternate JournalN Biotechnol
PubMed ID23031816