Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs

Alexey Stepanov, Alexander Belyy, Igor Kasheverov, Alexandra Rybinets, Maria Dronina, Igor Dyachenko, Arkady Murashev, Vera Knorre, Dmitry Sakharov, Natalya Ponomarenko, Victor Tsetlin, Alexander Tonevitsky, Sergey Deyev, Alexey Belogurov, Alexander Gabibov

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment. Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT. Conclusion: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBiotechnology Letters
DOIs
Publication statusAccepted/In press - 21 Apr 2016
Externally publishedYes

Fingerprint

Myelin-Oligodendrocyte Glycoprotein
Immunotoxins
Glycoproteins
Lymphocytes
Immunotherapy
Corynebacterium diphtheriae
B-Lymphocytes
Multiple Sclerosis
Diphtheria Toxin
Catalytic Antibodies
Lymphocyte Depletion
Pharmacokinetics
Lethal Dose 50
Autoantigens
Antibodies
Escherichia coli
Purification
Toxicity
Culture Media
Catalyst activity

Keywords

  • Diphtheria toxin
  • Immunotoxin
  • Myelin oligodendrocyte glycoprotein
  • Prokaryotic expression

ASJC Scopus subject areas

  • Biotechnology

Cite this

Stepanov, A., Belyy, A., Kasheverov, I., Rybinets, A., Dronina, M., Dyachenko, I., ... Gabibov, A. (Accepted/In press). Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs. Biotechnology Letters, 1-8. https://doi.org/10.1007/s10529-016-2092-5

Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs. / Stepanov, Alexey; Belyy, Alexander; Kasheverov, Igor; Rybinets, Alexandra; Dronina, Maria; Dyachenko, Igor; Murashev, Arkady; Knorre, Vera; Sakharov, Dmitry; Ponomarenko, Natalya; Tsetlin, Victor; Tonevitsky, Alexander; Deyev, Sergey; Belogurov, Alexey; Gabibov, Alexander.

In: Biotechnology Letters, 21.04.2016, p. 1-8.

Research output: Contribution to journalArticle

Stepanov, A, Belyy, A, Kasheverov, I, Rybinets, A, Dronina, M, Dyachenko, I, Murashev, A, Knorre, V, Sakharov, D, Ponomarenko, N, Tsetlin, V, Tonevitsky, A, Deyev, S, Belogurov, A & Gabibov, A 2016, 'Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs', Biotechnology Letters, pp. 1-8. https://doi.org/10.1007/s10529-016-2092-5
Stepanov, Alexey ; Belyy, Alexander ; Kasheverov, Igor ; Rybinets, Alexandra ; Dronina, Maria ; Dyachenko, Igor ; Murashev, Arkady ; Knorre, Vera ; Sakharov, Dmitry ; Ponomarenko, Natalya ; Tsetlin, Victor ; Tonevitsky, Alexander ; Deyev, Sergey ; Belogurov, Alexey ; Gabibov, Alexander. / Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs. In: Biotechnology Letters. 2016 ; pp. 1-8.
@article{7f7f44fb77e34fc8b148880ce5c98e12,
title = "Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs",
abstract = "Objective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment. Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT. Conclusion: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS.",
keywords = "Diphtheria toxin, Immunotoxin, Myelin oligodendrocyte glycoprotein, Prokaryotic expression",
author = "Alexey Stepanov and Alexander Belyy and Igor Kasheverov and Alexandra Rybinets and Maria Dronina and Igor Dyachenko and Arkady Murashev and Vera Knorre and Dmitry Sakharov and Natalya Ponomarenko and Victor Tsetlin and Alexander Tonevitsky and Sergey Deyev and Alexey Belogurov and Alexander Gabibov",
year = "2016",
month = "4",
day = "21",
doi = "10.1007/s10529-016-2092-5",
language = "English",
pages = "1--8",
journal = "Biotechnology Letters",
issn = "0141-5492",
publisher = "Springer Netherlands",

}

TY - JOUR

T1 - Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs

AU - Stepanov, Alexey

AU - Belyy, Alexander

AU - Kasheverov, Igor

AU - Rybinets, Alexandra

AU - Dronina, Maria

AU - Dyachenko, Igor

AU - Murashev, Arkady

AU - Knorre, Vera

AU - Sakharov, Dmitry

AU - Ponomarenko, Natalya

AU - Tsetlin, Victor

AU - Tonevitsky, Alexander

AU - Deyev, Sergey

AU - Belogurov, Alexey

AU - Gabibov, Alexander

PY - 2016/4/21

Y1 - 2016/4/21

N2 - Objective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment. Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT. Conclusion: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS.

AB - Objective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment. Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.5 mg per liter of culture medium. Recombinant DT-MOG was recognized in vitro by MOG-reactive antibodies and has catalytic activity comparable with wild-type DT. Conclusion: Enhanced pharmacokinetics (mean residence time in the bloodstream of 61 min) and minimized diminished nonspecific toxicity (LD50 = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS.

KW - Diphtheria toxin

KW - Immunotoxin

KW - Myelin oligodendrocyte glycoprotein

KW - Prokaryotic expression

UR - http://www.scopus.com/inward/record.url?scp=84964343985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964343985&partnerID=8YFLogxK

U2 - 10.1007/s10529-016-2092-5

DO - 10.1007/s10529-016-2092-5

M3 - Article

SP - 1

EP - 8

JO - Biotechnology Letters

JF - Biotechnology Letters

SN - 0141-5492

ER -