用于表达髓鞘少突胶质细胞糖蛋白特异性B细胞受体的自身反应性淋巴细胞免疫治疗的重组免疫毒素的研发。

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

作者信息

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

机构信息

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, Moscow, Russia, 117997.

Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Tatarstan, Russia.

出版信息

Biotechnol Lett. 2016 Jul;38(7):1173-80. doi: 10.1007/s10529-016-2092-5. Epub 2016 Apr 21.

DOI:10.1007/s10529-016-2092-5

PMID:27099070

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.

摘要