November 10, 2020
Monoclonal antibodies and cancer treatment: What to know
BY Devon Carter
Last updated Jan. 11, 2022.
First emerging almost three decades ago, monoclonal antibodies are changing the way doctors treat cancer and other illnesses, including COVID-19. These drugs mimic the immune system’s natural ability to fight off infection.
But how do monoclonal antibodies work to treat cancer? What are their side effects? And how are doctors using them to treat COVID-19? We spoke with Ecaterina Dumbrava, M.D., to learn more.
Monoclonal antibodies copy the benefit of natural antibodies
The immune system creates millions of y-shaped proteins called antibody receptors – or antibodies. Each antibody is floating through the body looking for a unique target that’s on the surface of a foreign cell called an antigen. When an antibody finds its target, it binds with the antigen and helps the immune system kill the diseased cell.
“An antibody is like a key that’s matched to a specific door,” says Dumbrava.
Monoclonal antibodies are drugs that are designed to copy the benefit of natural antibodies and their ability to fight off cancer and other illness.
How monoclonal antibodies are used to treat cancer
Monoclonal antibodies are used to treat many cancer types. They’re given to patients through an infusion and can be used alone or in combination with other cancer treatments. Each monoclonal antibody works in one or multiple ways, depending on the antigen that it’s targeting.
Some monoclonal antibodies directly bind to the cancer cells to kill them. Because they’re targeting specific receptors in the cells, these monoclonal antibodies are referred to as targeted therapies. An example is trastuzumab (Herceptin), which is used to treat HER2-positive breast cancer and stomach cancer.
“Trastuzumab attaches to the HER2 receptors on the cancer cells and prevents them from multiplying, which stops growth and slows cancer progression,” Dumbrava says.
Other monoclonal antibodies help improve the immune system’s response to cancer cells. These drugs are known as immunotherapy. An example is nivolumab, which targets the PD-1 receptor. It’s used to treat many cancer including, but not limited to, lung cancer, kidney cancer, melanoma, lymphoma and some head and neck cancers.
Immunotherapy drugs like nivolumab can sometimes cause severe side effects like inflammation in the colon or the lungs. “The immune system becomes too boosted and it attacks normal tissue,” Dumbrava says.
To manage the inflammation, the patient stops the immunotherapy and is given steroids. If the steroids don’t work, some patients may receive a different monoclonal antibody to bring the inflammation down. “It’s fascinating that we use monoclonal antibodies to treat side effects from other monoclonal antibodies,” Dumbrava says.
Engineering monoclonal antibodies to treat cancer more effectively
Monoclonal antibodies can also be modified further to be more effective. One approach is to create bi-specific antibodies. Instead of attaching to just a cancer cell, bi-specific antibodies attach to a cancer cell and a type of immune cell called a T cell.
Another approach is to attach a chemotherapy drug to a monoclonal antibody. These are called antibody-drug conjugates. “With this approach, chemotherapy is delivered to the cancer cells while avoiding healthy cells,” Dumbrava says. “It’s sort of like a trojan horse.” An example is trastuzumab emtansine, which combines the HER2 monoclonal antibody trastuzumab with the chemotherapy drug emtansine. When trastuzumab connects with HER2 antigen expressed on the cancer cells, emtansine enters inside the cancer cell and kills it.
CAR T cell therapy is also built off a monoclonal antibody known as chimeric antigen receptor (CAR). T cells are removed from a patient through a process like a blood draw. In the lab, Dumbrava says, the T cells are modified to produce the CAR, which allows the T cells to attach to specific antigens on the tumor cells. The engineered CAR T cells are then reinfused back into the patient. “The T cells are engineered to have the right key to unlock the door of the cancer cell and destroy it,” Dumbrava says.
While CAR T cell therapies are currently approved by the Food and Drug Administration (FDA) to treat some types of B-cell lymphoma, acute lymphoblastic leukemia and multiple myeloma, studies are underway to explore the use of CAR T cell therapy or similar therapies in solid tumors such as lung, breast or liver cancer.
Monoclonal antibody side effects vary, but are usually mild
When compared to chemotherapy, monoclonal antibodies are precise in the way they attack cancer cells. Fewer normal cells are being affected by the therapy, which results in fewer side effects.
However, Dumbrava says, there are still risks. Some of the most common mild side effects are fatigue, nausea, diarrhea and skin rashes. Some patients also have an allergic reaction to the infusion, so they may break out in hives or experience itching.
Side effects of monoclonal antibodies can be severe. Although it’s rare, the allergic reaction to the infusion can become life-threatening. Other rare but severe concerns include decreased blood cell counts, bleeding or problems with the heart or lungs.
Monoclonal antibodies now treat COVID-19
Cancer isn’t the only disease treated with monoclonal antibodies. They’re also used to treat chronic inflammatory diseases like Crohn’s disease and rheumatoid arthritis, as well as other diseases like graft-versus-host disease. Now, monoclonal antibodies are being used to treat the coronavirus (COVID-19).
“Similar to how we’ve identified antibodies for cancer, antibody targets on the coronavirus have also been identified,” Dumbrava says. Monoclonal antibodies help shorten the time of severe illness by preventing the infected cells from multiplying.
While these drugs directed at COVID-19 currently have emergency use authorization from the FDA, Drumbrava is optimistic for the future of monoclonal antibodies and envisions them as a backbone of future cancer treatment plans.
“I believe that we’re heading towards all patients receiving some form of immunotherapy during their treatment course,” Dumbrava. “It’s really a game-changer.”
Request an appointment online at MD Anderson or by calling 1-877-632-6789.
An antibody is like a key that’s matched to a specific door.
Ecaterina Ileana Dumbrava, M.D.