Abstract
Monoclonal antibody (MAB) conjugates with cytostatic agents (ADC) are intended for selective delivery of a cytostatic agent to a tumor cell. Three ADC have been approved for clinical use (gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab-DM1); a few dozens of other ADC are undergoing clinical trials. Several derivatives of natural substances (antibiotics and inhibitors of microtubules) having a high antitumor activity are used as cytostatic agents included in ADC. They are inapplicable in clinical practice as self-sustained drugs due to their considerable toxicity. Of great importance for the implementation of the ADC effect is the character of a linker connecting MAB with a cytostatic agent and ensuring selective intracellular release after ADC internalization. The structure, mechanisms of action, and the results of clinical trials of a number of ADC are considered here as an illustration (by way of example). The development of ADC can help introduce new effective cytostatic agents into clinical practice.
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