Antibody-drug conjugates (ADCs) represent a novel class of cancer therapy designed to specifically treat tumors while sparing healthy organs or tissue. They consist of three key components (Figure 1): a tumor specific antibody, a stable linker and a potent chemotherapeutic agent (also known as the warhead or toxin). The antibody component ensures the specific binding to cancer cells (by binding to proteins predominantly found on the outside of these cancerous cells); once bound, the ADC is taken up by the tumor cell and the toxin is released leading to the death of the cancer cell. The linker component connects the antibody to the toxin and ensures that the toxin is not released into the body before it has reached the inside of cancer cells to avoid or reduce side effects commonly seen with conventional chemotherapy1. Proteins that are predominantly found on the surface of cancer cells and to which the ADC binds are called cancer targets.
Figure 1: Simple schematic of an ADC
The development of ADCs is expanding rapidly with more than 50 molecules in different phases of clinical development for a wide variety of tumor indications2, and two ADCs have already been approved by the United States Food and Drug Administration3,4 and by the European Medicines Agency5,6.
ADC Therapeutics is a leader in the field of developing ADCs using the pyrrolobenzodiazepine (PBD) dimer platform. PBD dimers are a class of very potent toxins which are more active at killing cancer cells and have a different mode of action compared to warheads like maytansinoids or auristatins, commonly used in other ADCs like the ones already marketed7.