title: Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth.
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.
authors.affiliation: Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Behdani
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
authors.forename: Morteza
authors.initials: M
authors.lastname: Karimipour
authors.forename: Hossein
authors.initials: H
authors.lastname: Khanahmad
authors.forename: Steve
authors.initials: S
authors.lastname: Schoonooghe
authors.forename: Azam
authors.initials: A
authors.lastname: Aslemarz
authors.forename: Negar
authors.initials: N
authors.lastname: Seyed
authors.forename: Reza
authors.initials: R
authors.lastname: Moazami-Godarzi
authors.forename: Farzad
authors.initials: F
authors.lastname: Baniahmad
authors.forename: Mahdi
authors.initials: M
authors.lastname: Habibi-Anbouhi
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh-Ghassabeh
authors.forename: Serge
authors.initials: S
authors.lastname: Muyldermans
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D057809:HEK293 Cells; D006801:Humans; D000922:Immunotoxins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011994:Recombinant Proteins / Q000302:isolation & purification; D061905:Single-Domain Antibodies / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*; D037521:Virulence Factors / Q000494:pharmacology / Q000627:therapeutic use*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D011994:Recombinant Proteins; D061905:Single-Domain Antibodies; D040301:Vascular Endothelial Growth Factor Receptor-2; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A