CYS MARKS THE SPOT: Genentech’s THIOMAB strategy involves engineering cysteine residues into the antibody backbone to provide defined points for drug conjugation.COURTESY OF GENENTECHUntil relatively recently, chemotherapies for cancer have walked a precarious line between maximizing tumor cell death and minimizing toxicity. With few exceptions, physicians simply had no way to direct these potent drugs solely to where they were needed.
Now, they do. Using antibody-drug conjugates (ADCs), oncologists can aim a chemical payload at any cell for which they can identify a specific antigen, such as the HER2 receptor on breast cancer cells.
ADCs—tripartite structures in which antibodies are covalently joined to toxins via a linker—are the biological equivalent of a smart bomb. In theory, the configuration renders poisons inert as they circulate through the body, preventing them from doing harm until they are released and activated inside the targeted cell, and pharmaceutical companies have embraced the concept: dozens of ADCs are now in clinical trials, and two have been approved by the US Food and Drug Administration.
What does it take to make a good ADC? A good antibody and a potent drug, of ...
