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.

Original language	English
Pages (from-to)	93-96
Number of pages	4
Journal	Acta Naturae
Volume	7
Issue number	4
Publication status	Published - 2015
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Biochemistry
Biotechnology
Molecular Biology
Molecular Medicine

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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.

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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.}",

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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

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