COMPLEMENT IN PATHOLOGIES, POSSIBILITY OF CORRECTION USING A NOVEL HUMANIZED ANTIBODY THAT CAN BLOCK ALTERNATIVE PATHWAY OF COMPLEMENT SYSTEM ACTIVATION

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Abstract

Two monoclonal antibodies were developed and were shown to block the complement system alternative pathway (AP) activation at the stage of assembly and activation of C3 convertase. The humanized antibody hC34 specific to a binding site on α’2 determinant of С3с fragment inhibited in vitro the human complement activation by 90% at a dose of 3 μg/ml of blood serum. The antibody 3А8 specific to rat complement C3 component and similar to antibody hC34 was demonstrated to be pharmacologically active in model of closed craniocerebral injury (data of functional and histological studies). The results of this study indicate the humanized antibody hc34 to be promising for treatment of central nervous system pathologies and of other diseases associated with complement hyperactivation.

About the authors

N. P. Gorbunov

State Research Institute of Highly Pure Biopreparations

Author for correspondence.
Email: fake@neicon.ru

Junior Researcher, Laboratory of Protein Biochemistry,

Saint Petersburg

Russian Federation

A. V. Zhakhov

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Leading Researcher, Laboratory of Protein Biochemistry, 

Saint Petersburg

Russian Federation

A. V. Trofimov

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Group Leader, Laboratory of Protein Biochemistry,

Saint Petersburg

Russian Federation

K. A. Nekrasova

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Deputy Head of R&D Department, 

Saint Petersburg

Russian Federation

S. V. Rodin

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Group Leader, Laboratory of Protein Biochemistry,

Saint Petersburg

Russian Federation

E. A. Atanesyan

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Senior Researcher, Laboratory of Protein Biochemistry,

Saint Petersburg

Russian Federation

E. A. Karabanova

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Engineer, Laboratory of Protein Biochemistry,

Saint Petersburg

Russian Federation

M. S. Zakharov

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

Head of Department of Preclinical Studies, 

Saint Petersburg

Russian Federation

A. S. Simbirtsev

State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru

RAS Corresponding Member, MD, Professor, Scientific Supervisоr,

Saint Petersburg

Russian Federation

A. M. Ischenko

State Research Institute of Highly Pure Biopreparations

Email: a.m.ischenko@hpb.spb.ru

PhD, Head of Laboratory of Protein Biochemistry,

Saint Petersburg

Russian Federation

References

  1. Ricklin D., Mastellos D. C., Reis E. S., Lambris J. D. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018 Jan, 14(1), 26–47.
  2. Пат. РФ № 2630647: С07К 16/18, С12N15/00, A61K 39/395/ Картузова В. Е., Трофимов А. В., Ищенко А. М., Родин С. В., Жахов А. В., Симбирцев А. С., Климов Н. А., Петров А. В., Карасев М. М. – заявка 2016120997; опубл. 11.09.2017, Бюл. № 26.

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Copyright (c) 2019 Gorbunov N.P., Zhakhov A.V., Trofimov A.V., Nekrasova K.A., Rodin S.V., Atanesyan E.A., Karabanova E.A., Zakharov M.S., Simbirtsev A.S., Ischenko A.M.

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