Antibody–drug conjugates: targeted weapons against cancer

Abstract:

Antibody–drug conjugates (ADCs) are formed by a targeting antibody conjugated to a chemotherapeutic molecule through a linker. Recent data demonstrate that ADCs represent a valuable advancement for the clinics and, despite their recent appearance in medicine, they are already undergoing an innovation wave aimed at targeting all three ADC building blocks. Thus, new antibody formats are being engineered, site-specific linkers are being designed, and highly toxic molecules, like RNA polymerase inhibitors, are starting to be used for conjugation. These molecules were previously considered extremely toxic and could not be used as chemotherapeutic drugs. In this review, we will present an overview of current cancer treatments and their limitations, and the logic that has led to the generation of ADCs. Their mechanism of action will be outlined, and the most recent novelties in linker design and optimization will be discussed, along with present and near future discoveries in the current ADC research pipeline.

Keywords::

• immunoconjugates
• antibody–drug conjugates
• antibody fragments
• cancer
• monoclonal antibodies

Acknowledgments

LI is supported by a fellowship from the University of Pavia; CS’ salary comes from Ministry for Education, University and Research; LV has a European Fellowship from the School of Specialization in Clinical Pathology.

Disclosure

The authors report no conflicts of interest in this work.