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

• Корчагина, Анна Александровна
• кандидат биологических наук
• 2013

Оглавление диссертации кандидат биологических наук Корчагина, Анна Александровна

СПИСОК СОКРАЩЕНИЙ.

ГЛАВА I. ОБЗОР ЛИТЕРАТУРЫ.

Значение УЕОР112 для неопластического ангиогенеза и антиангиогенной терапии.

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

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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