Antibody–cytotoxic drug conjugates in clinical trials and future perspectives: the development of Trojan horses

Abstract

Chemotherapy and targeted agents, such as small molecules and monoclonal antibodies, have individually improved cancer medical therapeutics, yet there is still an unmet need for resistant or refractory disease. Drug combinations are usually more effective, but dose-limiting toxicities are of concern. The idea of developing a “smart bomb” treatment dates many years back. Nowadays, the development of biotechnology and the deeper knowledge of molecular biology have made possible the engineering of tumor-specific antibodies bearing cytotoxins directly and solely targeting the tumor cell, thus minimizing toxicity and increasing efficacy. Approved agents include trastuzumab emtansine (T-DM1) for breast cancer, brentuximab vedotin for Hodgkins’ disease, and gemtuzumab ozogamacin for relapsed acute myeloid leukemia. The present short review presents several newer antibody–drug conjugates (ADCs) in clinical studies and discusses ways to optimize ADC future design.