Оценка потенциальной иммуногенности рекомбинантных человеческих костных морфогенетических белков

Введение. Костные морфогенетические белки (BMPs) являются подгруппой суперсемейства белков трансформирующих фактор роста бета (TGF-β), где играют важную роль в формировании и восстановлении костной ткани. Рекомбинантные костные морфогенетические белки человека (rhBMPs) в настоящее время проходят клиническую оценку в эффективности усиления процессов регенерации костной ткани после травм и заболеваний опорно-двигательного аппарата. Клинические испытания сопровождались подробным определением безопасности с использованием анализов как in vitro, так и in vivo. Первоначально высказывались опасения по поводу иммуногенности некоторых терапевтических белков из-за их нечеловеческого происхождения. Однако белки, полученные из сыворотки или тканей человека, и продукты, полученные из рекомбинантной ДНК, такие как rhBMPs, идентичные или почти идентичные нативным человеческим белкам, также оказались иммуногенными. Цель работы – провести оценку возможных реакций со стороны иммунной системы при применении rhBMPs, уделяя особое внимание ADA и потенциальным стратегиям, направленным на минимизацию иммуногенности rhBMPs. Материалы и методы. Для всестороннего поиска оригинальных работ, обзоров литературы, клинических случаев и метаанализов, демонстрирующих возможные реакции со стороны иммунной системы при применении rhBMPs, использованы базы данных PubMed, Embase, Google Scholar, база Кокрановской библиотеки (Cochrane Database). Результаты. Проанализированы возможные реакции со стороны иммунной системы при применении rhBMPs как в клинических, так и в доклинических исследованиях. Было выявлено, что выработка антител является одним из побочных эффектов после применения rhBMPs. Тем не менее зарегистрированные случаи иммуногенности rhBMPs значительно различаются из-за отсутствия стандартизации методов. Заключение. В различных клинических испытаниях не наблюдались иммунологически связанные нежелательные явления, а образование антител никогда не оказывало отрицательного воздействия на формирование новой костной ткани и клинические исходы.

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