Рецептор фактора роста эндотелия сосудов второго типа: получение рекомбинантного препарата, моноклональных антител и системы направленного транспорта тема диссертации и автореферата по ВАК РФ 03.01.04, кандидат биологических наук Корчагина, Анна Александровна
- Специальность ВАК РФ03.01.04
- Количество страниц 120
Оглавление диссертации кандидат биологических наук Корчагина, Анна Александровна
СПИСОК СОКРАЩЕНИЙ.
ГЛАВА I. ОБЗОР ЛИТЕРАТУРЫ.
Значение УЕОР112 для неопластического ангиогенеза и антиангиогенной терапии.
Рекомендованный список диссертаций по специальности «Биохимия», 03.01.04 шифр ВАК
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Создание рекомбинантных антител против вируса клещевого энцефалита и изучение их свойств1999 год, кандидат биологических наук Николенко, Галина Николаевна
Разработка способов повышения эффективности клеточных противоопухолевых вакцин2007 год, кандидат биологических наук Бережной, Алексей Евгеньевич
Дизайн рекомбинантных антител2007 год, доктор биологических наук Тикунова, Нина Викторовна
Введение диссертации (часть автореферата) на тему «Рецептор фактора роста эндотелия сосудов второго типа: получение рекомбинантного препарата, моноклональных антител и системы направленного транспорта»
Структура рецепторов семейства УЕСР11.8
Биологические функции УЕСРКЛ.11
УЕСРЯ2 и его биологическая роль.12
Опухолевый ангиогенез.17
Ингибиторы УБОРЯ рецепторов в антиангиогенной терапии опухолей.21
Функциональное значение растворимых форм рецепторов.28
Резистентность опухолей к антиангиогенной терапии.31
Направленная доставка наноконтейнеров.36
Перспективы и заключение.38
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Заключение диссертации по теме «Биохимия», Корчагина, Анна Александровна
ВЫВОДЫ:
1. Клонирование в плазмиду рЕТ32а кДНК, кодирующей с I-III иммуноглобулин-подобные домены экстраклеточного фрагмента VEGFR2, позволило получить штамм E.coli Rosetta(DE3)pET32a/VEGFR2I-III продуцирующий VEGFR2i.m с выходом 13±2 мг/л.
2. Лиганд-рецепторный анализ, разработанный на основе непрямого твердофазного иммуноферментного анализа, позволяет определять VEGFR2 с пределом чувствительности 4±0,5 нг/мл.
3. Иммунизация мышей рекомбинантным препаратом VEGFR2I-III позволила получить В-лимфоциты селезенки, способные при слиянии с клетками миеломной культуры Sp2/0-Agl4 образовывать гибридные клетки, продуцирующие моноклональные антитела к VEGFR2I-III, характеризующиеся константой аффинности - 1,8±0,12*108 М"1.
4. Моноклональные антитела к VEGFR2 обладают способностью ингибировать миграцию глиомных клеток на 56±4% в тесте повреждения монослоя клеток глиомы С6 (wound healing test).
5. Ковалентная конъюгация моноклональных aHTH-VEGFR2 антител с блок-иономерными наногелями (диаметр 100±10 нм) на основе ПЭГ-б-ПМАК, объективно повышали специфичность их накопления в клетках интракраниальной опухоли при внутривенном введении.
Благодарности.
Автор выражает благодарность научному руководителю Владимиру Павловичу Чехонину за помощь на протяжении всей диссертационной работы, Наталье В. Нуколовой и Татьяне Сандаловой за помощь в работе с наногелями, Анне В. Леопольд за советы в наработке и очистке рекомбинантного УЕСРЯ2, Надежде Е. Волгиной за помощь в работе к культурой НиУЕС, Владимиру Павловичу Баклаушеву за помощь в освоении иммунохимических, Ольге Ивановне Гуриной и Сергею А. Шеину за помощь в освоении гибридомной технологии получения моноклональных антител, Мельникову Павлу за помощь в лазерной конфокальной микроскопии, Надежде Филипповне Гриненко за помощь в работе с культурами клеток, Клавдии Павловне Ионовой и сотрудникам вивария за помощь в работе с животными, Кристине В. Новиковой и Карине Ш. Кардашовой за помощь в работе с клетками глиомы Сб.
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