Antibody-drug conjugation linkage (ADC) is a technique that combines genetically engineered monoclonal antibodies with cancer-killing drugs. In the July issue of the journal Nature Biotechnology, researchers report a novel ADC technique with potential for cancer treatment that promises to reduce the damage drugs cause to healthy cells with fewer side effects. While acutely recognizing cancer cells, antibodies that target tumors can also ignore normal cells, a characteristic of antibodies used in the development of targeted drug delivery, and the researchers hope to bind chemotherapeutic drugs to such antibodies to form ADC drugs. Previous methods of making ADC drugs have had a variety of mixing effects, with some antibodies carrying more of the drug than others, making it difficult to determine the optimal amount of drug to use. Now, William Mallet and coworkers at Genentech in the US have developed a new method for manufacturing ADC drugs that can determine the amount of drug carried. Compared to previous methods, chemotherapeutic drugs are bound to antibodies in a reproducible way, so there are fewer side effects on healthy cells. They modified special sites in the structure of the antibody to facilitate drug binding without affecting the overall structure of the antibody or its ability to recognize cancer cells. Studies in model mice showed that this new ADC drug was more effective than traditional ADC drugs: only half the dose killed as many cancer cells. And, in rabbits and monkeys, they tolerated the new ADC drug better, meaning the drug had fewer side effects in people.