Unfortunately, few of the body’s 100 million naturally occurring antibodies are able to recognize cancer cells. To overcome this problem, researchers have developed ways of finding antibodies that have a specific receptor needed to work against different cancers. These are called “monoclonal antibodies” because they are of a single type that is grown in large quantities for cancer therapy.
Some antibodies target cancer directly to kill tumor cells. This approach works best against blood cancers, where rituximab (Rituxan®) is probably the most widely used antibody therapy. Rituxan kills B-cell-derived cancers such as non-Hodgkin’s lymphoma or chronic lymphocytic leukemia.
Radioimmunotherapy is a technique developed at Fred Hutchinson Cancer Center over the last 20 years to help blood cancer patients who don’t respond to chemotherapy or who, more recently, may have stopped getting benefit from Rituxan. In the 1990s, Oliver W. Press, MD, PhD, and Frederick R. Appelbaum, MD, among others, pioneered the idea of using antibodies as biological vehicles to target radiation directly to cancer cells and thereby limit the amount of radiation that goes to healthy organs. Their work led to the subsequent development of two FDA-approved radioimmunotherapy drugs, Zevalin and Bexxar.
What Kind of Cancers can be Treated with Antibody Therapy?
While the use of radioimmunotherapy is presently confined to blood cancers, researchers have found that monoclonal antibodies selected to block key growth signals for cancer cells can be effective against solid tumors. Well-known monoclonal antibody drugs in this category include trastuzumab (Herceptin®), used to treat breast cancer, and bevacizumab (Avastin®), which is used to treat colorectal, lung, brain, kidney, and ovarian cancers.
Checkpoint Inhibitors Block Antibodies that Hide Cancer Cells from the Immune System
More recently, monoclonal antibodies have been developed that manipulate anti-tumor T-cell responses by blocking negative regulatory proteins on T-cells. These monoclonal antibodies are called immune checkpoint inhibitors. Fred Hutch was one of the first institutions in the world to research checkpoint inhibitor immunotherapy in patients. Dr. Shailender Bhatia and Dr. John Thompson were instrumental in the clinical trials of two checkpoint inhibitors, anti-PD-1 and anti-PD-L1, to treat melanoma. This research helped to develop two recent FDA-approved checkpoint inhibitor drugs — pembrolizumab (Keytruda®) and nivolumab (Opdivo®) — that are now used to treat melanoma, lung cancer, head and neck cancers and other cancers.
Finally, monoclonal antibodies can be modified to carry a toxic substance directly to targeted tumor cells. These are called antibody-drug conjugates (ADCs). The conjugates are the attached poisons, which can be a chemotherapy drug or cell toxin. In this manner, drugs that might be toxic to normal cells can be delivered only to tumor cells without the side effects that would be caused by the drug alone. Several experimental antibody-drug conjugates are currently under study in ongoing clinical trials that are part of the Fred Hutch Phase I clinical trials program.
