Sometimes the challenge in making a medicine is not hitting the intended target in unhealthy tissue, but avoiding it, or related targets, in healthy tissue. A molecule’s lack of selectivity in some cases causes side effects that may limit the dose of a medicine a person can safely receive, or rule out that molecule altogether.
“The field has certainly gotten much more sophisticated in engineering large molecules with enhanced or brand new properties. What hasn’t really kept pace is the ability to limit activity to the desired location in the body,” says Paul Carter, Genentech Fellow, Antibody Engineering.
Scientists are navigating this by building in specificity from the very beginning of the drug discovery and optimization process. “It’s not just coming up with the molecule and taking it from an idea to a drug. It’s about solving all of these problems: how do you deliver it, how do you target it and how do you formulate it?” says Sarah Hymowitz, Vice President & Principal Scientist, Protein Sciences.
One established method that we use for drug delivery is harnessing antibodies. Antibodies bind a unique protein, making them well-suited for engaging a specific target in the body. Bispecific antibodies take this one step further. These medicines can bind two different targets at the same time and can be uniquely designed for different therapeutic needs. For example, we are working to develop bispecific antibodies that can bring together tumor cells and immune cells to help the immune system detect and destroy cancer.
Beyond antibody-based drugs, targeted therapies of all modalities could be of great value to patients who may not be able to withstand an effective dose of medicine like chemotherapy. Or they may serve as adjuncts, or add-ons, to therapies like checkpoint immunotherapy, that currently work only in a subset of patients. The discovery and development of targeted therapies can help us achieve our goal of widening the circle of effective treatment so that we can continue to overcome more challenging drug targets and reach as many people in need as possible.