Inhibition of neovascularisation in human endothelial cells using anti NRP-1 nanobody fused to truncated form of diphtheria toxin as a novel immunotoxin. (4th March 2021)

• Record Type: Journal Article
• Authors: Naderi, Shamsi; Roshan, Reyhaneh; Behdani, Mahdi; Kazemi-Lomedasht, Fatemeh
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 43:Number 2(2021)
• Page Start: 230
• Page End: 238
• Publication Date: 2021-03-04
• Subjects: Immunotoxin -- diphtheria toxin -- targeted cancer therapy -- NRP-1 -- VHH; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2021.1888114
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: Neuropilin-1 (NRP-1) regulates a range of physiological and pathological processes, including angiogenesis. Targeting of NRP1 is considered a significant approach in cancer therapy. In the present study, a novel antiNRP1 immunotoxin (αNRP1 IT) was developed by genetic fusion of a single domain (VHH) anti-NRP-1 antibody fragment to a truncated diphtheria toxin. The αNRP1 IT was expressed into bacterial cells as an inclusion body (IB). Expression of αNRP1 IT was confirmed by SDS-PAGE and western blotting. Recombinant αNRP1 IT was purified using nickel affinity chromatography. Toxicity and antiangiogenesis effect of αNRP1 IT was investigated both in vitro and in vivo . Results showed that αNRP1 IT significantly reduced the viability of human umbilical vein endothelial cell line (HUVEC) ( p < .05). The αNRP1 IT significantly inhibited tube formation of HUVEC cells ( p < .001). Furthermore, αNRP1 IT inhibited angiogenesis in Chick Chorioallantoic Membrane (CAM) Assay. These data suggest the potential of αNRP1 IT as a novel therapeutic in targeted cancer therapy.