Antibody–drug conjugates (ADCs) are a unique class of targeted immuno-oncology therapeutics that combine the tumor-targeting selectivity, stability, and favorable pharmacokinetic profile of monoclonal antibodies, with the potent antitumor activity of cytotoxic drugs. The ultimate goal of ADCs is to increase the therapeutic index of potent chemical agents, by the selective delivery of the chemotherapy to the tumor, whilst sparing the healthy tissues.
The concept of ADCs is not new and the first attempts at developing them started in the 90s. However, the field witnessed a lot of project failures requiring scientists to go back to the drawing board to tackle several challenges:
- create plasma-stable linkers to avoid premature release of the drug that is associated with non-specific toxicity,
- identify and enable the use of more potent cytotoxic drugs,
- find conjugation methods (to attach the drugs to the antibody) leading to homogeneous ADCs (same number of drugs on each antibody), in order to optimize both the tolerability and efficacy profiles.
The biggest challenge of ADCs is, in the end, to obtain a favorable therapeutic index for patients.