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
N1 - Funding Information:
This work was supported by the Russian Scientific Foundation grant 14-24-00106. We thank Dr. Yury Belyi (Gamaleya Research Institute, Russia) for a plasmid coding for the A-subunit of DT. A.S. obtained personal support from RFBR, research project No. 15-34-70037 mol_a_mos.
Publisher Copyright:
© 2016, Springer Science+Business Media Dordrecht.
PY - 2016/7/1
Y1 - 2016/7/1
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 - https://www.scopus.com/pages/publications/85027944681
U2 - 10.1007/s10529-016-2092-5
DO - 10.1007/s10529-016-2092-5
M3 - Article
C2 - 27099070
AN - SCOPUS:85027944681
SN - 0141-5492
VL - 38
SP - 1173
EP - 1180
JO - Biotechnology Letters
JF - Biotechnology Letters
IS - 7
ER -