UAB works to improve immunotherapy in treating gynecologic cancers

Immunotherapy is a common type of treatment that uses the patient’s own immune system to fight cancer and other diseases. Gynecologic cancers are treated in different ways, but immunotherapy is becoming more common in treating cervical cancer, uterine (endometrial) cancer, and other cancers that start in women’s reproductive organs. At the O’Neal Comprehensive Cancer Center at UAB, physicians and researchers are improving the use of certain immunotherapies, and many patients are seeing better treatment results.

The different kinds of immunotherapies work in different ways. Some help the immune system locate the cancer cells to better attack them, while others strengthen the immune system or find ways to get around the defenses that cancer cells have.

Gynecologic cancer is caused by the rapid growth and spread of abnormal cells in a woman’s reproductive organs, which include the uterus, cervix, ovaries, vagina, and vulva. In the past, treatments usually involved removing or destroying the cancer cells through a combination of surgery, radiation, and chemotherapy. Even when these treatments reduced the amount of cancerous tumor in the body, sometimes the cells from which tumors grow remained in place, and over time they became resistant to chemotherapy and radiation.

UAB Medicine patient Alicite Lewis, 45, of Uniontown, Ala., was diagnosed with cervical cancer in 2015. After her initial diagnosis, she was referred to Charles A. (Trey) Leath III, M.D., director of the UAB Division of Gynecologic Oncology. “In February of 2016, I began radiation and chemotherapy at UAB,” Lewis said. “After two years, we still were not seeing any success. I went through several treatments before we found a solution, when Dr. Leath explained to me that there was another method we could try. Of course, at that time, I was willing to try anything.”

Finding the invader

The method of therapy Lewis would receive is a type of immunotherapy that uses medication to boost the immune system, to help the body better detect and destroy cancer cells. As part of its normal function, the immune system detects and destroys abnormal cells, and this likely prevents or reduces the growth of many cancers.

Research shows that cancer cells can “escape” the immune system through genetic changes that make them less visible. In other cases, cancer cells may survive because of proteins on their surface that turn off immune cells, or they may alter normal cells around the tumor to interfere with how the immune system responds to the cancer cells.

Immunotherapy medications fight those cancer cells by using proteins to start or increase the immune response. Some immunotherapy drugs, such as monoclonal antibodies, work in more than one way to control cancer cells. This is also known as targeted therapy, because the antibodies block a specific protein on the cancer cell to keep it from growing.

An important feature of the immune system is its ability to avoid attacking the body’s normal cells. To do this, it uses “checkpoint” proteins found on immune cells that need to be “switched” on or off to start an immune response. Unfortunately, cancer cells sometimes use these checkpoints to get around being attacked by the immune system. Drugs that help prevent this “end run” around the immune system are known as checkpoint inhibitors. Dr. Leath says that this part of the immunotherapy process is like identifying a hidden invader.

“Many cancers can influence the body’s immune system so that there’s no awareness of the cancer’s presence,” Dr. Leath said. “In that situation, the system is still doing the right thing by keeping the cell-fighting mechanism off, so that healthy cells are not harmed. In a manner of speaking, immunotherapy turns the immune system back on, and then the cancer gets exposed and identified, allowing the system to work toward eradicating it.”

In Lewis’ case, the method was very successful. Every six weeks, she received intravenous infusions of a drug that targets PD-1, a protein on T cells that normally helps keep them from attacking other cells in the body. By blocking PD-1, the infusions boosted her immune response against cancer cells and shrank the tumor. Lewis says it saved her life.

“The best news I got was when I learned that tumor had not grown,” Lewis said. “Then it got smaller. After the last treatment, my status changed to ‘under observation.’ I look at my situation and know it could have been worse. It took a while to find this solution, but immunotherapy saved my life. Through my treatment, I meet people who have cancer and I share my experience with them. I hope they think, ‘Well, if she can get through this at stage 4, maybe I can, too,’ and that they will continue to try new approaches with their medical team. I call my own medical team my UAB family, and this family helped me have a life. It’s not a completely normal life, but it’s a life I wouldn’t have without their care.”

Research goals

Immunotherapy has not yet shown success in treating all types of cancer, but UAB Medicine continues to study and improve these treatments as common and effective ways to battle the disease. As with chemotherapy and radiation, researchers also are working to limit the side effects. Boosting the immune system with immunotherapy drugs can cause the body to target healthy cells as well as cancer cells. The extent of the side effects depends on the patient’s overall health before treatment, the type of gynecologic cancer, how advanced it is, and the type of therapy used.

Dr. Leath says the overall goal is to combine different immunotherapies with radiation and chemotherapy and better target cancer cells by customizing treatments for specific types of cancer and certain groups of patients.

“Switching on immune systems is not like using a dimmer switch,” Dr. Leath said. “On is on, so it can impact any organ system. But through research, we are finding ways to reduce that. In fact, a major part of our research mission is to determine which immunotherapies are best suited to patients according to their specific cases and then to better customize treatment plans. We have participated in several clinical trials that have helped advance immunotherapy overall.”

Click here to learn more about immunotherapy at the O’Neal Comprehensive Cancer Center at UAB, and click here to learn more about immunotherapy research and experimental treatments.

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