An antibody that becomes active only when it encounters tumours could provide a path to safer cancer drugs.

Although gentler than other cancer drugs, side effects from antibodies still limit the dosage that patients can receive. To reduce toxicity, Henry Lowman of CytomX, a biotechnology firm in South San Francisco, California, and his colleagues designed a covert antibody — a protein-based molecule that cannot bind to its target until it faces protein-cleaving enzymes that are often abundant near tumours.

In mice, a covert antibody against a cancer-promoting protein called epidermal growth factor receptor showed little activity in the blood, yet fought tumours at levels similar to the cancer drug cetuximab. The antibody was also less toxic than cetuximab in monkeys.

Sci. Transl. Med. 5, 207ra144 (2013)