Helping the Immune System Treat Cancer
Immunotherapy, also called biologic therapy or biotherapy, uses the body’s own defenses to fight cancer. Clinical trials of immunotherapy are now accepting people with breast cancer; they are small and in early phases, and focus on metastatic disease.
Though immunotherapies are not likely to change practice in breast cancer in the near future, they are an exciting area of research that could have an impact on treatment down the road.
“I think patients have always been interested in immunotherapy,” says Douglas Yee, MD, a medical oncologist and a professor and director of the Masonic Cancer Center at the University of Minnesota. “Women are very interested in the idea that maybe we can try a different strategy to treat their breast cancer besides our conventional targeted therapies or chemotherapies.”
When she first learned about immunotherapy, Shauntell Cullen, 35, from Boise, Idaho, was excited. Shauntell was diagnosed with metastatic breast cancer in 2012. She received different chemotherapies and tamoxifen, but the disease grew despite these treatments. After two-and-a-half years, Shauntell asked her doctor to help her find clinical trials that might halt the cancer’s spread.
A Hot Topic
The immune system is a complex group of organs and cells that defend the body against infections and other foreign substances.
Its complicated nature, and the difficulty it has noticing cancer cells, which are often similar enough to healthy cells to stop it from reacting, made breakthroughs difficult in the past.
But excitement surrounding immunotherapy has appeared again in the last decade or so because of a new idea that has gained momentum about how the immune system may respond to cancer.
Think of the immune system as a car with brakes. Brakes are useful, because they stop the car from crashing. They keep the immune system from attacking substances that aren’t harmful. But the brakes can also stop the car from going full speed, keeping the immune system from using its power to fight cancer cells. Dr. Yee says the idea that doctors may be able to help the immune system fight cancer by “removing the brakes” is a big part of the new buzz around immunotherapy.
“We’ve learned that tumor cells are very efficient at applying the brakes to the immune system,” Dr. Yee says. “We’re learning how to overcome some of those brakes with new molecules that really help us have a more effective immune response against tumor cells.”
Today, immunotherapy shows the most potential in diseases like lung cancer and a kind of skin cancer called melanoma, Dr. Yee says. That’s because those cancers have many complex mutations, or changes in cell DNA. More mutations mean a better chance of helping the immune system recognize and respond to cancer.
Breast cancer, especially hormone receptor-positive breast cancer, tends to have fewer mutations than those other cancers, so it “has been a little slower to come to immunotherapy,” Dr. Yee says.
Research continues into immunotherapy for all types of breast cancer, but there is especially great potential for triple-negative breast cancer. That’s because of all of the subtypes, triple-negative has the highest number of mutations.
In October 2014, Shauntell started receiving treatment as part of an immunotherapy study that includes people with a variety of metastatic cancers. Shauntell was the first person with breast cancer to enter the trial.
“It’s pretty exciting to be the first—and scary at the same time to be the first,” Shauntell says.
Types of Immunotherapy
Researchers are looking at different types of immunotherapies. These treatments all use the power of the immune system, but do it in different ways. They include:
Medicines that work by removing the brakes that stop the immune system from fighting cancer are called checkpoint inhibitors. They interact with substances that appear on cancer cells, especially the PD-1 and PDL-1 proteins, to rev up the immune system. Checkpoint inhibitors being studied in breast cancer include pembrolizumab (Keytruda), MPDL3280A and indoximod.
Vaccines, whether for the flu or for cancer, have the same goal: create an immune response to help the body fight a harmful substance. In breast cancer, though, because the disease is not known to be caused by a virus, vaccines are used for treatment rather than prevention. Vaccines can be made from the person’s own tumor cells or from the tumor cells of someone else. Once an injection is given, the vaccine can strengthen the immune system and help it recognize cancer cells as harmful, foreign substances. Vaccines being studied in breast cancer include NeuVax, GVAX and GP2.
T cells, a kind of white blood cell, protect the body from disease. T cells can be removed and grown in a lab to make more than the body could make on its own and make them better at fighting cancer. Then, they are put back inside the body.
One T-cell therapy technique involves putting chimeric antigen receptors, or CARs, on the T cells. These receptors attach themselves to proteins on cancer cells, killing the cancer.
Another technique involves tumor-infiltrating lymphocytes, or TILs, white blood cells that may exist deep inside tumors. This is the technique involved in Shauntell’s treatment. The cells were taken out of her body and adapted in the lab, with the hope that when put back in, they would help her immune system fight the cancer. The treated white blood cells, given the nickname “cancer fighting ninjas,” were returned to Shauntell’s body in February.
You may be familiar with monoclonal antibodies. That’s because trastuzumab (Herceptin), used to treat HER2-positive breast cancer, is from this family of medicines. Monoclonal antibodies are proteins made in a lab. They treat cancer in a variety of ways. Trastuzumab, for example, attaches to HER2 proteins and blocks the signals that tell cancer cells to grow.
Some monoclonal antibodies also help the immune system see cancer it may not have noticed otherwise. So far, trastuzumab has not been used with that purpose in mind. But recent research suggests some people who benefit from trastuzumab may have an immune response to the treatment.
“That’s very interesting and it’s an area that we as breast cancer physicians are just starting to understand,” Dr. Yee says.
Joining a Trial
It can be a challenge to enter an immunotherapy trial. The trials need people whose cancers have specific traits, and there are limited trials in only a few places.
Shauntell’s trial is held at the National Institutes of Health, in Bethesda, Maryland. She travels the more than 2,000 miles from Boise every few weeks for checkups. Preparing for the procedure, which involves chemotherapy treatment, receiving her new white blood cells and getting her white blood cell counts high enough to prevent infection, once required a 30-day stay in the hospital.
Though she feels lucky to be able to make the journey, Shauntell says it’s still hard. She has to leave her young son behind. And though she has not yet had serious side effects, her treatment comes with a risk of high fever and dangerously low blood pressure immediately after the white blood cells are put back inside the body.
Shauntell also had to accept the idea of stopping other, more well-known treatments to start a treatment whose value is unknown. But she feels taking part in the trial is the right decision for her—whether the treatment works or not.
“There’s a big part of me that honestly feels like I was just meant to be here, [participating in this trial],” she says. After so many other treatments, “I felt that I needed to shock my cancer. Standard chemotherapies … they just weren’t working. So for me to have something completely different—if my body can fight this off, I just have that much better of a chance of living longer.”
At the end of March, Shauntell learned the liver tumors had shrunk by 5 to 10 percent.
If you are interested in learning more about joining a clinical trial for immunotherapy, talk to your doctor and visit ClinicalTrials.org or cancerresearch.org/cancer-immunotherapy/clinical-trial-finder.