Crotamine-based recombinant immunotoxin targeting HER2 for enhanced cancer cell specificity and cytotoxicity

Toxicon. 2023 Jul:230:107157. doi: 10.1016/j.toxicon.2023.107157. Epub 2023 May 15.

Abstract

Crotamine, one of the major toxins present in the venom of the South American rattlesnake Crotalus durissus terrificus, exhibits potent cytotoxic properties and has been suggested for cancer therapy applications. However, its selectivity for cancer cells needs to be improved. This study designed and produced a novel recombinant immunotoxin, HER2(scFv)-CRT, composed of crotamine and single-chain Fv (scFv) derived from trastuzumab targeting human epidermal growth factor receptor 2 (HER2). The recombinant immunotoxin was expressed in Escherichia coli and purified using various chromatographic techniques. The cytotoxicity of HER2(scFv)-CRT was assessed in three breast cancer cell lines, demonstrating enhanced specificity and toxicity in HER2-expressing cells. These findings suggest that the crotamine-based recombinant immunotoxin has the potential to expand the repertoire of recombinant immunotoxin applications in cancer therapy.

Keywords: Breast cancer cell lines; Crotamine; HER2; Maltose-binding protein; Trastuzumab.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Crotalid Venoms* / chemistry
  • Crotalus
  • Humans
  • Immunotoxins* / metabolism
  • Neoplasms* / drug therapy

Substances

  • Crotalid Venoms
  • crotamine
  • Immunotoxins