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- Title
Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs.
- Authors
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
- 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 (LD = 1.76 mg/kg) of the DT-MOG makes it a potential candidate for the immunotherapy of MS.
- Subjects
MYELIN oligodendrocyte glycoprotein; MULTIPLE sclerosis; AUTOANTIGENS; LYMPHOCYTES; ANTIBODY-toxin conjugates
- Publication
Biotechnology Letters, 2016, Vol 38, Issue 7, p1173
- ISSN
0141-5492
- Publication type
Article
- DOI
10.1007/s10529-016-2092-5