Novel recombinant immunotoxin of EGFR specific nanobody fused with cucurmosin, construction and antitumor efficiency in vitro

Oncotarget. 2017 Jun 13;8(24):38568-38580. doi: 10.18632/oncotarget.16930.

Abstract

Epidermal growth factor receptor (EGFR) overexpression is related to the increased aggressiveness, metastases, and poor prognosis in various cancers. In this study, we successfully constructed a new EGFR nanobody-based immunotoxin rE/CUS containing cucurmosin (CUS), The immunotoxin was expressed by prokaryotic system and we obtained a yield of 5 mg protein per liter expression medium. The percentage of it's binding ability totumor cell lines A549, HepG2, SW116, which highly expressed EGFR was 55.6%, 79.6% and 97.1%, respectively, but SW620 was only 4.45%. rE/CUS has the ability to bind A549, HepG2, SW116 cells specifically, and the antigen binding capability was not affected because of extra part of CUS component. The rE/CUS significantly inhibited the cell viability against EGFR over expression tumor cell lines in a dose-and time-dependent manner. Moreover, rE/CUS also induced apoptosis of HepG2 and A549 mightily. Our results demonstrate that rE/CUS is a potential therapeutic strategy for treating EGFR-positive solid tumors.

Keywords: EGFR; cucurmosin; immunotoxins; nanobody.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Immunotoxins / pharmacology*
  • Plant Proteins / pharmacology*
  • Single-Domain Antibodies / pharmacology*

Substances

  • Immunotoxins
  • Plant Proteins
  • Single-Domain Antibodies
  • cucurmosin protein, Cucurbita moschata
  • EGFR protein, human
  • ErbB Receptors