Immunoconjugates as drugs of targeted oncotherapy

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Abstract

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.

About the authors

S. D. Shceglov

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: stepanshceglov@mail.ru
ORCID iD: 0009-0002-0777-0422

Stepan D. Shceglov

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

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