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Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs
Authors
Belogurov A.
Belyy A.
+13 more
Deyev S.
Dronina M.
Dyachenko I.
Gabibov A.
Kasheverov I.
Knorre V.
Murashev A.
Ponomarenko N.
Rybinets A.
Sakharov D.
Stepanov A.
Tonevitsky A.
Tsetlin V.
Publication date
1 January 2016
Publisher
Abstract
© 2016, Springer Science+Business Media Dordrecht.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
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Last time updated on 07/05/2019