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

Mahdi Behdani (1) , Sirous Zeinali (1) , Morteza Karimipour (1) , Hossein Khanahmad (1, 2) , Steve Schoonooghe (3, 4) , Azam Aslemarz (1) , Negar Seyed (1) , Reza Moazami-Godarzi (1) , Farzad Baniahmad (1) , Mahdi Habibi-Anbouhi (1) , Gholamreza Hassanzadeh-Ghassabeh (3, 4) , Serge Muyldermans (4, 5)

1 Biotechnology Research Center
2 Department of Genetics and Molecular Biology
3 VUB - Vrije Universiteit Brussel
4 Laboratory of Cellular and Molecular Immunology
5 Department of Structural Biology

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.

Mots clés: VEGFR2-specific Nanobody; Pseudomonas exotoxin A; tumor cell growth

Domaines: Génétique

Mahdi Behdani, Sirous Zeinali, Morteza Karimipour, Hossein Khanahmad, Steve Schoonooghe, et al.. Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth.. New Biotechnology, 2013, 30 (2), pp.205-9. ⟨10.1016/j.nbt.2012.09.002⟩. ⟨pasteur-00821222⟩