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Вопросы гематологии/онкологии и иммунопатологии в педиатрии

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Роль моноклональных антител в терапии лимфопролиферативных заболеваний

https://doi.org/10.24287/1726-1708-2015-14-2-20-37

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Аннотация

Разработка моноклональных антител (МАТ) для лечения гемобластозов является одной из наиболее быстро развивающихся областей науки. В настоящее время известно несколько антител (АТ), эффективных в лечении острого лимфобластного лейкоза (ОЛЛ) у детей. В то время как неконъюгированные гуманизированные АТ хорошо переносятся и могут применяться в сочетании с химиотерапией, иммуноконъюгаты (АТ, связанные со вторичной молекулой -токсином, радиоизотопом или меткой), доставляющие токсичные соединения непосредственно в клетки-мишени обладают более серьезными нежелательными явлениями. Антигены (АГ), обладающие высокой избирательной экспрессией на патологических клетках, являются идеальными мишенями для АТ, их использование в настоящее время изучается в ходе I/II и III фаз клинических исследований при ОЛЛ у детей. АГ, стабильно экспрессируемые на мембране клетки (CD19, CD52), являются субстратом для биспецифических Т-клеточных АТ (bi-specific T-cell engagers - BiTEs) или для неконъюгированных АТ, реализующих свой механизм действия через АТ-зависимую клеточную (antibody-dependent cellular cytotoxity - ADCC) и комплемент-зависимую цитотоксичность (complement-dependent cytotoxity -CDC). АГ, подвергающиеся быстрой интернализации (CD22, CD5 и CD7), являются подходящими мишенями для иммуноконъюгатов, которые доставляют токсические вещества непосредственно в клетки-мишени путем специфического связывания. Для различных АГ, экспрессированных только в определенных подгруппах ОЛЛ (CD20, CD33, CD2, CD3, CD4), существуют эффективные соединения, которые могут быть использованы в лечении пациентов с рефрактерными формами лейкоза. МАТ обладают совершенно иным механизмом антилейкемического действия по сравнению с обычной химиотерапией и, конечно, существенно изменят стратегию лечения детей с ОЛЛ в будущем.

Об авторах

Arend Von Stackelberg
Charité-Universitaetsmedizin Berlin
Россия


Ксения Игоревна Романова
Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России
Россия


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Для цитирования:


Von Stackelberg A., Романова К.И. Роль моноклональных антител в терапии лимфопролиферативных заболеваний. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2015;14(2):20-37. https://doi.org/10.24287/1726-1708-2015-14-2-20-37

For citation:


Von Stackelberg A..., Romanova K.I. Role of monoclonal antibodies in therapy of lymphoproliferative disorders. Pediatric Hematology/Oncology and Immunopathology. 2015;14(2):20-37. (In Russ.) https://doi.org/10.24287/1726-1708-2015-14-2-20-37

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