Targeted antibodies are a form of cancer immunotherapy treatment that can disrupt cancer cell activity and alert the immune system to target and eliminate cancer cells.
Antibodies are proteins that are naturally produced by a type of immune cell called B cells and serve to protect us against a variety of threats, such as bacteria, viruses, and cancer cells. Antibodies do this by precisely targeting and binding to cell surface markers known as antigens.
On its own, our immune system has the ability to make trillions of different types of antibodies. Now, scientists can supplement our immune system by creating and customizing antibodies against specific cancer targets in the lab. These are often referred to as monoclonal antibodies due to their identical structure.
Most targeted antibodies are referred to as “passive” immunotherapies because they target tumor cells directly rather than immune cells; however, more recent innovations have produced variations of targeted antibodies that are considered “active” immunotherapies because they target immune cells, too. (See bispecific antibodies below for more on these.) Due to their cancer-targeting properties, many different targeted antibodies are currently being evaluated, both alone and in combination with other treatments, in a variety of cancer types in clinical trials.
"Naked" Monoclonal Antibodies (mAbs)
Once antibodies bind to cancer cells, they can disrupt pathways that are important to cancer cell activity, like those that allow them to grow uncontrollably (direct killing by the “front” end). These antibodies can also signal to other immune cells to eliminate the cancer cells (immune-mediated killing by the “back” end).
In 1997, the U.S. Food and Drug Administration (FDA) approved the first antibody for the treatment of cancer—the monoclonal antibody rituximab (Rituxan®) for leukemia—and since then, over a dozen more have received FDA approval.
Antibody-Drug Conjugates (ADCs)
More recently, advances in technology have enabled the development of new antibody-based immunotherapies. One such approach is antibody-drug conjugates (ADCs), in which a targeted antibody is equipped with anti-cancer drugs, so that when the antibody targets and binds to cancer cells, it also delivers a toxic drug that can kill the cancer cells. By delivering these chemotherapeutic drugs directly to tumors, it can potentially reduce the side effects associated with indiscriminate deployment of these toxic components.
Another new type of antibody-based immunotherapy that has been developed is bispecific antibodies. These are made by taking the targeting front end regions of two different antibodies and combining them to create a product that can bind to two different targets. Some bispecific antibodies, known as bispecific T cell engagers, or BiTEs, target both cancer cells and immune cells known as T cells.
These BiTEs work to bring T cells into close proximity with—and enable them to eliminate—cancer cells. Due to their ability to target immune cells directly, these BiTEs are considered “active” immunotherapies. The first bispecific antibody—a BiTE called blinatumomab (Blincyto®)—was approved by the FDA in 2014 for subsets of patients with leukemia. Other bispecific antibodies have been developed to target different cancer antigens.