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.

journal_name

Biotechnol Lett

journal_title

Biotechnology letters

authors

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 Jr,Gabibov A

doi

10.1007/s10529-016-2092-5

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

1173-80

issue

7

eissn

0141-5492

issn

1573-6776

pii

10.1007/s10529-016-2092-5

journal_volume

38

pub_type

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