Prospects for the Use of Antibody-Drug Conjugates in Cancer Therapy

Abstract

Today, cancer continues to be one of the most dangerous diseases, annually causing the deaths of more than 9 million people in the world. Therefore, new and more effective methods of cancer therapy are in demand. As monoclonal antibody-based immunotherapy has already shown its effectiveness, antibody-drug conjugates (ADC), one of its successful variants, have significant and not yet fully realized potential. ADCs are monoclonal antibodies bound to cytotoxic drugs through linkers. In many clinical trials and already in standard clinical practice, ADCs have demonstrated significant advantages over the combination therapy with unmodified antibodies and chemotherapeutic drugs. Due to new achievements in the field of molecular immunology and biotechnology, the potential of ADCs is assessed as a breakthrough, which will allow ADCs to become the most sought-after anticancer drugs in the coming years. Owing to ADCs it has become possible to deliver drugs to tumor cells in a targeted manner without significant toxic effects on healthy tissues and organs. To date, 15 ADC drugs have been approved worldwide for use in clinic, and more than a hundred more drugs of this class are at various stages of clinical trials. At the same time, ADC therapy is associated with certain side effects and limited efficacy. Therefore there is a need to develop more advanced conjugates. This review describes the history of the development of ADC as a therapeutic class of molecules, their structure, targets, and mechanism of action. It also outlines the prospects and directions for further development of ADCs.