Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press144910.17650/1726-9784-2024-23-2-36-46REVIEWОБЗОР ЛИТЕРАТУРЫImmunoconjugates as drugs of targeted oncotherapyИммуноконъюгаты как препараты таргетной онкотерапииhttps://orcid.org/0009-0002-0777-0422ShceglovS. D.ЩегловС. Д.
Russian Federation

Stepan D. Shceglov

24 Kashirskoe Shosse, Moscow 115522

Степан Дмитриевич Щеглов 

115522 Москва, Каширское шоссе, 24

stepanshceglov@mail.ruN. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава России2606202423236462606202426062024https://bioterapevt.abvpress.ru/jour/article/view/1449

Chemotherapy for cancer is associated with a significant risk of severe side effects due to the effects of cytostatics on healthy cells. Targeted oncotherapy is an innovative approach to cancer treatment that targets specific protein structures and metabolic pathways that are highly likely to be inherent in tumor cells. Historically, immunoconjugates (IC) were among the first targeted therapy agents, along with monoclonal antibodies, to be approbated and subsequently approved for clinical use. Traditionally, an IC is described as a monoclonal antibody covalently linked to a therapeutic component via a linker. Due to their vector component, these drugs allow the application of selective effects on epitope-defined targets, which significantly increases the therapeutic index of highly toxic antitumor agents. In addition, targeting therapy helps to overcome drug resistance of tumors and improve the prognosis of the disease. Herewith, the pharmaceutical design of IC requires comprehensive consideration of specific aspects such as physicochemical properties of the conjugated substance, optimal choice of immunoglobulin class G isotype, biochemical properties of the linker and conjugation methods. A comprehensive study of these aspects will not only optimize the design of IC, but will also contribute to the widespread use in clinical practice and expand the range of applications of such drugs. This review presents the evolution of the antibody – drug conjugate concept in the context of the application of these drugs in oncotherapy. The aspects of structure and specific features of strategies of drug-drug conjugation with monoclonal antibody, which are basic for IC design, are also discussed and summarized.

Химиотерапия онкологических заболеваний сопряжена со значительным риском развития тяжелых побочных эффектов вследствие воздействия цитостатиков на здоровые клетки организма. Таргетная онкотерапия представляет собой инновационный поход к лечению онкологических заболеваний, направленный на специфические белковые структуры и метаболические пути, с высокой долей вероятности присущие опухолевым клеткам. Исторически одними из первых препаратов таргетной терапии, наряду с моноклональными антителами, были апробированы и в дальнейшем одобрены для клинического применения иммуноконъюгаты (ИК). Традиционно ИК описывается как ковалентно связанное с терапевтическим компонентом через линкер моноклональное антитело. За счет векторного компонента данные препараты позволяют применять избирательное воздействие на определенные эпитопы мишени, что значительно повышает терапевтический индекс высокотоксичных противоопухолевых средств. В дополнение к этому таргетная терапия способствует преодолению лекарственной устойчивости опухолей и улучшению прогноза заболевания. При этом фармацевтическая разработка ИК требует всестороннего учета специфических аспектов, таких как физико-химические свойства конъюгируемого вещества, оптимальный выбор изотипа иммуноглобулина класса G, биохимические свойства линкера и методы конъюгации. Всестороннее исследование этих аспектов позволит не только оптимизировать дизайн ИК, но и будет способствовать широкому распространению в клинической практике и расширению спектра применения подобных препаратов. В данном обзоре представлена эволюция концепции «конъюгат антитело – лекарственное средство» в рамках применения данных препаратов в онкотерапии. Рассматриваются и обобщаются также базовые для дизайна ИК аспекты строения и особенности стратегий конъюгации лекарственного вещества с моноклональным антителом.

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