HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis

Evgeniya Sokolova, Evgeniy Guryev, Andrey Yudintsev, Vladimir Vodeneev, Sergey Deyev, Irina Balalaeva

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody as a targeting module and fragment of Pseudomonas exotoxin A as an effector (toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer cells overexpressing HER2 receptor in vitro and on HER2-positive experimental tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of particular importance in the case of targeted therapeutic agent aimed at personalizing treatment of disease in relation to molecular genetic characteristics of each patient. After specific binding to HER2 on the cell surface and clathrin-mediated endocytosis the immunotoxin passes through retrograde trafficking route. During this route the immunotoxin molecule is supposed to undergo enzymatic processing that ends in separation of C-terminal and N-terminal fragments of the immunotoxin. Finally, C-terminal functionally active fragment of 4D5scFv-PE40 arrests protein synthesis in cytoplasm followed by cell death via apoptosis.

Original languageEnglish
Pages (from-to)22048-22058
Number of pages11
JournalOncotarget
Volume8
Issue number13
DOIs
Publication statusPublished - 2017
Externally publishedYes

Fingerprint

Immunotoxins
Apoptosis
Clathrin
Poisons
Endocytosis
Recombinant Proteins
Molecular Biology
Neoplasms
Cytoplasm
Cell Death
Antibodies
Therapeutics
Proteins

Keywords

  • 4D5scFv
  • HER2
  • PE40
  • Pseudomonas aeruginosa exotoxin A
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology

Cite this

HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis. / Sokolova, Evgeniya; Guryev, Evgeniy; Yudintsev, Andrey; Vodeneev, Vladimir; Deyev, Sergey; Balalaeva, Irina.

In: Oncotarget, Vol. 8, No. 13, 2017, p. 22048-22058.

Research output: Contribution to journalArticle

Sokolova, Evgeniya ; Guryev, Evgeniy ; Yudintsev, Andrey ; Vodeneev, Vladimir ; Deyev, Sergey ; Balalaeva, Irina. / HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis. In: Oncotarget. 2017 ; Vol. 8, No. 13. pp. 22048-22058.
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