Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors

E. A. Sokolova, O. A. Stremovskiy, T. A. Zdobnova, I. V. Balalaeva, S. M. Deyev

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Recombinant immunotoxins are extremely promising agents for the targeted therapy of tumors with a certain molecular profile. In this work, we studied the properties of a new recombinant HER2-specific immunotoxin composed of the scFv antibody and a fragment of Pseudomonas exotoxin A (4D5scFv-PE40). High affinity of the immunotoxin for the HER2 tumor marker, its selective cytotoxicity against HER2-overexpressing cells, and its storage stability were demonstrated. The 50% inhibitory concentration (IC50) of the 4D5scFv-PE40 immunotoxin for HER2-overexpressing cancer cells was 2.5-3 orders of magnitude lower compared to that for CHO cells not expressing this tumor marker and was 2.5-3 orders of magnitude lower than IC50 of free PE40 for HER2-overexpressing cancer cells. These findings provide a basis for expecting in the long run high therapeutic index values of the 4D5scFv-PE40 immunotoxin for its use in vivo.

Original languageEnglish
Pages (from-to)93-96
Number of pages4
JournalActa Naturae
Volume7
Issue number4
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

Immunotoxins
Tumors
Inhibitory Concentration 50
Neoplasms
Tumor Biomarkers
Cells
Therapeutics
Single-Chain Antibodies
Immunoglobulin Fragments
CHO Cells
Cytotoxicity

Keywords

  • 4D5scFv
  • HER2 tumor marker
  • Pseudomonas exotoxin A
  • Recombinant immunotoxin
  • Targeted therapy

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Molecular Medicine

Cite this

Sokolova, E. A., Stremovskiy, O. A., Zdobnova, T. A., Balalaeva, I. V., & Deyev, S. M. (2015). Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors. Acta Naturae, 7(4), 93-96.

Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors. / Sokolova, E. A.; Stremovskiy, O. A.; Zdobnova, T. A.; Balalaeva, I. V.; Deyev, S. M.

In: Acta Naturae, Vol. 7, No. 4, 2015, p. 93-96.

Research output: Contribution to journalArticle

Sokolova, EA, Stremovskiy, OA, Zdobnova, TA, Balalaeva, IV & Deyev, SM 2015, 'Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors', Acta Naturae, vol. 7, no. 4, pp. 93-96.
Sokolova EA, Stremovskiy OA, Zdobnova TA, Balalaeva IV, Deyev SM. Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors. Acta Naturae. 2015;7(4):93-96.
Sokolova, E. A. ; Stremovskiy, O. A. ; Zdobnova, T. A. ; Balalaeva, I. V. ; Deyev, S. M. / Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors. In: Acta Naturae. 2015 ; Vol. 7, No. 4. pp. 93-96.
@article{4584b9d2b7514c2e8702568add915dd8,
title = "Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors",
abstract = "Recombinant immunotoxins are extremely promising agents for the targeted therapy of tumors with a certain molecular profile. In this work, we studied the properties of a new recombinant HER2-specific immunotoxin composed of the scFv antibody and a fragment of Pseudomonas exotoxin A (4D5scFv-PE40). High affinity of the immunotoxin for the HER2 tumor marker, its selective cytotoxicity against HER2-overexpressing cells, and its storage stability were demonstrated. The 50{\%} inhibitory concentration (IC50) of the 4D5scFv-PE40 immunotoxin for HER2-overexpressing cancer cells was 2.5-3 orders of magnitude lower compared to that for CHO cells not expressing this tumor marker and was 2.5-3 orders of magnitude lower than IC50 of free PE40 for HER2-overexpressing cancer cells. These findings provide a basis for expecting in the long run high therapeutic index values of the 4D5scFv-PE40 immunotoxin for its use in vivo.",
keywords = "4D5scFv, HER2 tumor marker, Pseudomonas exotoxin A, Recombinant immunotoxin, Targeted therapy",
author = "Sokolova, {E. A.} and Stremovskiy, {O. A.} and Zdobnova, {T. A.} and Balalaeva, {I. V.} and Deyev, {S. M.}",
year = "2015",
language = "English",
volume = "7",
pages = "93--96",
journal = "Acta Naturae",
issn = "2075-8251",
publisher = "Park Media Ltd.",
number = "4",

}

TY - JOUR

T1 - Recombinant immunotoxin 4D5scFv-PE40 for targeted therapy of HER2-positive tumors

AU - Sokolova, E. A.

AU - Stremovskiy, O. A.

AU - Zdobnova, T. A.

AU - Balalaeva, I. V.

AU - Deyev, S. M.

PY - 2015

Y1 - 2015

N2 - Recombinant immunotoxins are extremely promising agents for the targeted therapy of tumors with a certain molecular profile. In this work, we studied the properties of a new recombinant HER2-specific immunotoxin composed of the scFv antibody and a fragment of Pseudomonas exotoxin A (4D5scFv-PE40). High affinity of the immunotoxin for the HER2 tumor marker, its selective cytotoxicity against HER2-overexpressing cells, and its storage stability were demonstrated. The 50% inhibitory concentration (IC50) of the 4D5scFv-PE40 immunotoxin for HER2-overexpressing cancer cells was 2.5-3 orders of magnitude lower compared to that for CHO cells not expressing this tumor marker and was 2.5-3 orders of magnitude lower than IC50 of free PE40 for HER2-overexpressing cancer cells. These findings provide a basis for expecting in the long run high therapeutic index values of the 4D5scFv-PE40 immunotoxin for its use in vivo.

AB - Recombinant immunotoxins are extremely promising agents for the targeted therapy of tumors with a certain molecular profile. In this work, we studied the properties of a new recombinant HER2-specific immunotoxin composed of the scFv antibody and a fragment of Pseudomonas exotoxin A (4D5scFv-PE40). High affinity of the immunotoxin for the HER2 tumor marker, its selective cytotoxicity against HER2-overexpressing cells, and its storage stability were demonstrated. The 50% inhibitory concentration (IC50) of the 4D5scFv-PE40 immunotoxin for HER2-overexpressing cancer cells was 2.5-3 orders of magnitude lower compared to that for CHO cells not expressing this tumor marker and was 2.5-3 orders of magnitude lower than IC50 of free PE40 for HER2-overexpressing cancer cells. These findings provide a basis for expecting in the long run high therapeutic index values of the 4D5scFv-PE40 immunotoxin for its use in vivo.

KW - 4D5scFv

KW - HER2 tumor marker

KW - Pseudomonas exotoxin A

KW - Recombinant immunotoxin

KW - Targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=84952013373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952013373&partnerID=8YFLogxK

M3 - Article

VL - 7

SP - 93

EP - 96

JO - Acta Naturae

JF - Acta Naturae

SN - 2075-8251

IS - 4

ER -