Targeting direct hits to cancer cells

Advances in the treatment of cancer have been remarkable in the past decade. For many cancer types, chemotherapy remains the standard of care. The problem is that chemotherapy is delivered in a way that damages not only cancer cells but also healthy ones.
 
A deepening understanding of the biology of tumors has given rise to new compounds that target specific tumors at the molecular level. That, combined with innovative technologies to deliver those drugs, aims to reduce the impact of chemotherapy on healthy cells.
 
The pursuit of more targeted therapies includes the development of antibody drug conjugates (ADCs), a platform AbbVie has been working to advance with partner Seattle Genetics since 2011.
 
“Antibodies are very targeted molecules, and each binds to a specific protein in the body,” says Jochen Salfeld, Ph.D., vice president of global biologics discovery, based at the AbbVie Bioresearch Center in Worcester, Massachusetts. “The goal with antibody drug conjugates is to deliver a medicine to diseased tissue in a precise way that does not damage the healthy tissue.”

Each ADC has three parts – the antibody, which targets a particular protein; the toxin, which is meant to attack the diseased tissue; and a chemical that connects the two, called a linker. The linker is important because it allows the toxin to be released only once it reaches the target cell.
 
In addition to reducing the impact of chemotherapy on healthy cells, ADCs may also reduce the amount of drug needed for treatment.
 
“To be effective against cancer cells, the drug itself has to be very toxic. By directly focusing the drug to the cancer cell, we would reduce the amount of drug circulating in the body,” Salfeld says. “It’s essentially enhancing the drug’s effects inside of the cancer cell while using less drug overall.”
 
The ADC platform could also breathe life into molecules that are too toxic to be given on their own. “If we introduce them into a cell via an ADC, they may have a very different profile because the compound is specifically directed to the diseased tissue,” Salfeld says.
 

Seeking cancer cells