The safety, toxicology, and regulation of antibody-drug conjugates

Interviewer: Prof. Veysel Kayser, thank you very much for your time today. In this interview, we would like to discuss critical aspects of the safety and toxicology of antibody-drug conjugates (ADCs), and the revolving regulatory landscape. Can we start with a broad overview of ADCs in cancer: what they are and how they work? What are their key advantages and disadvantages compared to other cancer therapies such as chemotherapy and immunotherapy? Dr. Kayser: Sure! Antibody-drug conjugates are an advanced and relatively new type of cancer therapy that combines the target specificity of a monoclonal antibody with a potent cytotoxic agent—usually a small-molecule chemotherapeutic drug. They selectively kill cancer cells while sparing healthy tissues, thereby improving their therapeutic window compared to conventional chemotherapy. ADCs are composed of three main components that are the monoclonal antibodies (mAbs), the linker, and the cytotoxic drug, which is usually called the payload. The concept is not actually new, it dates back to Paul Ehrlich's magic bullet theory in the early 1900s. He proposed that therapeutic agents could specifically target disease-causing organisms and the idea laid the foundation of monoclonal antibody therapy, including ADCs. However, the first ADC, as we know it today, was described in literature in the '60s. But the concept was realized only in the '80s when the first ADC clinical trial was conducted in 1983.