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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Immunology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Immunology</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский иммунологический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1028-7221</issn><issn publication-format="electronic">2782-7291</issn><publisher><publisher-name xml:lang="en">Russian Society of Immunology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">290</article-id><article-id pub-id-type="doi">10.31857/S102872210006712-8</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">COMPLEMENT IN PATHOLOGIES, POSSIBILITY OF CORRECTION USING A NOVEL HUMANIZED ANTIBODY THAT CAN BLOCK ALTERNATIVE PATHWAY OF COMPLEMENT SYSTEM ACTIVATION</article-title><trans-title-group xml:lang="ru"><trans-title>КОМПЛЕМЕНТ ПРИ ПАТОЛОГИЯХ, ВОЗМОЖНОСТЬ КОРРЕКЦИИ С ПОМОЩЬЮ НОВОГО ГУМАНИЗИРОВАННОГО АНТИТЕЛА, БЛОКИРУЮЩЕГО АЛЬТЕРНАТИВНЫЙ ПУТЬ</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Gorbunov</surname><given-names>N. P.</given-names></name><name xml:lang="ru"><surname>Горбунов</surname><given-names>Н. П.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Junior Researcher, Laboratory of Protein Biochemistry,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>м. н. с. лаборатории биохимии белка,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zhakhov</surname><given-names>A. V.</given-names></name><name xml:lang="ru"><surname>Жахов</surname><given-names>А. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Leading Researcher, Laboratory of Protein Biochemistry, </p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>в. н. с. лаборатории биохимии белка,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Trofimov</surname><given-names>A. V.</given-names></name><name xml:lang="ru"><surname>Трофимов</surname><given-names>А. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Group Leader, Laboratory of Protein Biochemistry,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>руководитель группы лаборатории биохимии белка,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Nekrasova</surname><given-names>K. A.</given-names></name><name xml:lang="ru"><surname>Некрасова</surname><given-names>К. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Deputy Head of R&amp;D Department, </p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>зам. начальника отдела организации НИР,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Rodin</surname><given-names>S. V.</given-names></name><name xml:lang="ru"><surname>Родин</surname><given-names>С. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Group Leader, Laboratory of Protein Biochemistry,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>руководитель группы лаборатории биохимии белка,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Atanesyan</surname><given-names>E. A.</given-names></name><name xml:lang="ru"><surname>Атанесян</surname><given-names>Е. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Senior Researcher, Laboratory of Protein Biochemistry,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>с. н. с. лаборатории биохимии белка,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Karabanova</surname><given-names>E. A.</given-names></name><name xml:lang="ru"><surname>Карабанова</surname><given-names>Е. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Engineer, Laboratory of Protein Biochemistry,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>инженер 1 категории лаборатории биохимии белка,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zakharov</surname><given-names>M. S.</given-names></name><name xml:lang="ru"><surname>Захаров</surname><given-names>М. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Head of Department of Preclinical Studies, </p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>начальник отдела доклинических исследований,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Simbirtsev</surname><given-names>A. S.</given-names></name><name xml:lang="ru"><surname>Симбирцев</surname><given-names>А. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>RAS Corresponding Member, MD, Professor, Scientific Supervisоr,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>член-корреспондент РАН, д. м. н., профессор, научный руководитель,</p><p>Санкт-Петербург</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Ischenko</surname><given-names>A. M.</given-names></name><name xml:lang="ru"><surname>Ищенко</surname><given-names>А. М.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD, Head of Laboratory of Protein Biochemistry,</p><p>Saint Petersburg</p></bio><bio xml:lang="ru"><p>к. б. н., начальник лаборатории биохимии белка,</p><p>197110.Санкт-Петербург, ул. Пудожская, д. 7</p></bio><email>a.m.ischenko@hpb.spb.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">State Research Institute of Highly Pure Biopreparations</institution></aff><aff><institution xml:lang="ru">ФГУП «Государственный научно-исследовательский институт особо чистых биопрепаратов» Федерального медико-биологического агентства</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2019-07-15" publication-format="electronic"><day>15</day><month>07</month><year>2019</year></pub-date><volume>22</volume><issue>2-2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>754</fpage><lpage>756</lpage><history><date date-type="received" iso-8601-date="2020-06-03"><day>03</day><month>06</month><year>2020</year></date><date date-type="accepted" iso-8601-date="2020-06-03"><day>03</day><month>06</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 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.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2019, Горбунов Н.П., Жахов А.В., Трофимов А.В., Некрасова К.А., Родин С.В., Атанесян Е.А., Карабанова Е.А., Захаров М.С., Симбирцев А.С., Ищенко А.М.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="en">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.</copyright-holder><copyright-holder xml:lang="ru">Горбунов Н.П., Жахов А.В., Трофимов А.В., Некрасова К.А., Родин С.В., Атанесян Е.А., Карабанова Е.А., Захаров М.С., Симбирцев А.С., Ищенко А.М.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://rusimmun.ru/jour/article/view/290">https://rusimmun.ru/jour/article/view/290</self-uri><abstract xml:lang="en"><p>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.</p></abstract><trans-abstract xml:lang="ru"><p>Получены два моноклональных антитела, блокирующих активацию комплемента по альтернативному пути (АП) на этапе сборки и активации С3 конвертазы. Гуманизированное антитело hC34, специфичное сайту связывания на участке α’2 фрагмента С3с, ингибировало активацию комплемента человека на 90% in vitro в дозе 3 мкг/мл сыворотки крови. Антитело 3А8, специфичное С3 компоненту комплемента крысы и аналогичное антителу hC34, обладало фармакологической активностью в модели ЗЧМТ, что подтверждалось функциональным и гистологическим исследованием. Полученные результаты указывают на перспективность применения гуманизированного антитела hС34 для лечения патологий центральной нервной системы и других заболеваний с гиперактивацией комплемента.</p></trans-abstract><kwd-group xml:lang="en"><kwd>complement</kwd><kwd>alternative pathway of complement system activation</kwd><kwd>monoclonal antibodies</kwd><kwd>central nervous system pathologies</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>комплемент</kwd><kwd>альтернативный путь активации комплемента</kwd><kwd>моноклональные антитела</kwd><kwd>патологии центральной нервной системы</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>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.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>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.</mixed-citation></ref></ref-list></back></article>
