ПРИНЦИПЫ И ПРОБЛЕМЫ СУИЦИДНОЙ ГЕННОЙ ПРОТИВООПУХОЛЕВОЙ ТЕРАПИИ

DOI: https://doi.org/10.29296/24999490-2018-06-03

Е.Р. Немцова, доктор биологических наук, О.А. Безбородова, доктор биологических наук, Р.И. Якубовская, доктор биологических наук, профессор, А.Д. Каприн, академик РАН, доктор медицинских наук, профессор Московский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Российская Федерация, 125284, 2-й Боткинский пр., д. 3 E-mail: nemtz@yandex.ru

Представлен обзор литературы по суицидной генной противоопухолевой терапии. Метод основан на трансфекции опухолевых клеток конструкцией с геном фермента, способного превратить субстрат – малотоксичное пролекарство в высокотоксичный противоопухолевый агент. В обзоре рассмотрены современные представления о генно-терапевтических системах для этого вида лечения, требования к генной конструкции – эффекторному гену, промотору, к субстрату – пролекарству, описаны наиболее перспективные системы доставки генетического материала в клетки – вирусные и невирусные, рассмотрены условия реализации «эффекта свидетеля» – механизма, способствующего увеличению эффективности противоопухолевого и антиметастатического действия систем. Приведены данные о клинических испытаниях наиболее изученных систем «тимидинкиназа вируса простого герпеса (ВПГ) – ганцикловир» и «цитозиндезаминаза – 5-фторцитозин». Представлены результаты собственных исследований in vitro и in vivo бицистронной конструкции, в которой эффекторные гены тимидинкиназы ВПГ и гранулоцитарно-макрофагального колониестимулирующего фактора включены в плазмиду под конституциональным цитомегаловирусным промотором, а в качестве системы доставки использован невирусный вектор – блоксополимер полиэтиленимина с полиэтиленгликолем, к которому присоединен ТАТ-пептид. Доказаны продукция фермента и цитокина в трансфицированных конструкцией опухолевых клетках, цитотоксическое и противоопухолевое действие системы «тимидинкиназа ВПГ – ганцикловир» на различных моделях in vitro и in vivo и безопасность ее применения.

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