The Race to Make a Vaccine for Breast Cancer

It was not a complete surprise that Karen Lynch was diagnosed with breast cancer at 44 years old. Her father had cancer and died from it, as did her five sisters. My mother passed away from Pancreatic Cancer. It wasn't until nine years after her diagnosis and treatment with lumpectomy and radiation that Lynch discovered she had a genetic susceptibility to cancer. She decided to have a bilateral mastectomy and hysterectomy to reduce her risk of having another cancer.

Since I was 54, Lynch had no problem with the procedure. It was difficult to wrap my head around having a preventive mastectomy, even though my doctors said it wasn't a case of, " will you get breast cancer again, but when?" After considering and researching for three years, Lynch decided to have the surgery and live a long, healthy life.

She wants to do even more. She is a patient at Penn Medicine where she is being treated for breast cancer. It was an easy decision to join the trial if there was a vaccine that would prevent her from having cancer again. I want my children to have this vaccine so they won't have to worry about it.

Modern medicine refers to vaccines as the miracle of modern medicine because they can target the immune system against diseases. Cancer is one of the conditions that have long plagued humanity.

Robert Vonderheide is the director of the Abramson Cancer Center at Penn Medicine. It isn't a concept that's completely new.

The vaccine for cancer exists. Human papillomaviruses (HPV) vaccines can be used to prevent certain types of cancer. Most types of cancer aren't caused by Viruses, so the holy grail would be to train the body to recognize tumors. immunizing people who have already been diagnosed with cancer is one of the ways that researchers are looking at. New drug therapies that target the genetic changes that cause cancer have changed the way doctors treat the disease, thanks to improvements in the accuracy and speed of genetic decoding. The immune system can be trained to seek out and destroy cancer cells.

To date, these immunotherapy treatments have mostly been focused on patients with advanced disease that has spread throughout their bodies, and vaccines to target those widespread cancer cells have been a last resort to control the disease. The idea of a vaccine that could prevent cancer has been made more realistic due to the limited success of such vaccines.

Increasingly, scientists are using vaccines to treat cancer earlier, and they have started to score some victories in training the immune system to attack lung, skin, and kidneys cancers to prevent them from returning in recovered patients.

The strategies haven't worked for breast cancer. According to Vonderheide, a lot of breast tumors don't attract the immune system. The vaccine is designed to start an immune response that can be elaborated.

Vonderheide wants to use vaccines to improve the immune response against cancer by training cells to recognize tumors as foreign. Vonderheide believes that it may be possible to prevent people from getting cancer in the first place if they have already had it.

Breast cancer advocates say that a breakthrough can happen soon. Fran Visco, president of the National Breast Cancer Coalition, was diagnosed with breast cancer in 1987, but she was not treated differently than other patients. There is a lot of focus on immunotherapy and that is exciting. It hasn't changed women's lives yet.

The rate of breast cancer in the U.S. began to rise again in the 2000s, after holding steady for the past 50 years. 43,000 people are killed by breast cancer each year.

It is our belief that a vaccine approach is the key to preventing breast cancer in the first place.

The idea is to identify what is foreign in the tumors as much as possible and to create a vaccine that targets what is foreign. The immune response can be used to shrink or prevent cancer.

This type of vaccine may be at least a decade away because it is difficult to do. Cancer cells are normal cells that have picked up abnormal genetic messages and are starting to divide. It's difficult to identify the specific abnormality that cancer cells pick up since they're often tightly woven with non-cancerous features It was disappointing to attempt to target such cancer-specific genes in the past.

Clues about which cancer-causing genes are on the surface of tumors are provided by more sophisticated analyses of their genetics. Scientists have a better chance of training people's immune systems to recognize and target those "foreign" cancer markers if they have that knowledge.

The Cleveland Clinic is going to enroll women with early stages of triple negative breast cancer to receive a vaccine that will reduce their risk of developing advanced disease. The disease is called triple-negative because it is hard to treat because the cancer cells don't have any of the main genes. The doctors want to treat women at high risk of the disease, but who have not yet been diagnosed, with a vaccine to lower their chances of getting cancer.

The other end of the breast cancer spectrum was the focus of a vaccine being worked on by Knutson and Dr. Amy Degnim. Women with an early form of breast cancer called ductal carcinoma in situ are the first to be tested. In recent years, experts have debated whether or not DCIS is a form of breast cancer since it involves the ducts of the breast and doesn't spread to the rest of the breast. In the U.S., about 51,000 women are diagnosed with the disease each year, and some of them will become cancer. There is some evidence that a lot of DCIS may not progress to become cancer, but we don't know if that's true or not. The risk of developing cancer is why many women with the condition choose to have radiation and surgery. "Maybe we can scale back our treatments if the immune system could be trained to attack the disease."

The vaccine was given to people with advanced breast cancer first so that it could be tested on people with less advanced breast cancer. The approach was justified by the encouraging immune responses seen in that study.

The team is giving a vaccine to 43 women in a trial. All of the women will be treated with surgery to remove their DCIS, and Degnim and Knutson will look for signs of immunity. Blood samples will be taken to determine if the patients mounted an immune response against the DCIS.

A vaccine to prevent breast cancer is one step closer to being a reality. Scientists have a better idea of how tumors affect the immune system. Cancer cells protect themselves from the immune cells by throwing up a wall of protection. Immune suppression allows tumors to grow and spread undetected from one tissue to another.

Doctors were able to break down that wall. Cancer cells are exposed for the immune system to see and attack by drugs called immune checkpoint inhibitor. New hope in immunizing people against cancer can be found in combining these drugs with a vaccine. The first chance that we will see a vaccine approved is probably going to be in combination with an immune checkpoint inhibitors, says Knutson. The question of how effective the vaccine might be will be answered in real time if the tumor shrinks.

There are other targets for a cancer vaccine. The genes of breast cancer cells are also related. The most successful COVID-19 shots, from Moderna and Pfizer-bioNTech, used genetic material from the CoV-2 virus to build immunity, and scientists think a similar approach, using the genetic material DNA, could work for breast cancer.

If this vaccine can change the course of breast cancer for future generations, that's what Lynch is hoping for. One of her daughters was diagnosed with breast cancer at a young age and decided to have both breasts removed. She had fertility treatments to improve her chances of having a baby later in life. Lynch wants her children and their children to be safe. Lynch joined the trial at Penn Medicine in February to look at the safety of a vaccine against breast cancer. Cancer cells and cells that are less active in normal functioning are the most active cells. A vaccine that includes snippets of DNA coding for key parts of telomerase trains a group of immune cells in the body to find and destroy cancer cells that use too much telomerase. They talk the blood to kill the cancer cells. Training the T cells against cancer could be critical to making an effective breast cancer vaccine. He says that the best vaccines for cancer will be those that generate T cells, because those responses could last longer and generate a surge of immune cells. The study is part of Penn's new Basser Cancer Interception Institute which is focused on intervening in BRCA1 and BRCA2 cancers as early as possible to alter the normal progression of disease

Lynch is one of 16 people at Penn Medicine who have been diagnosed with cancer and who have the genes that put them at higher risk of developing breast cancer, so the team is trying to figure out if vaccinations will lower their chance of getting the disease again. 28 people with the genetic risk, but who have not yet been diagnosed with cancer, will be studied to see if the vaccine lowers their risk. Lynch will provide blood for Domchek and her team for nearly two years after completing her injections.

If the vaccine can reduce the risk of cancer, it will be a game-changer. Some women choose to have a preventative mastectomy if they are found to be carrying the breast cancer-causing genes. Because of the lack of an effective way to screen for ovarian cancer, some women choose to have their ovaries removed, which causes early menopause. There are not a lot of options for women with breast cancer. The idea of using the immune system to change the history of people is very important.

Scientists are cautiously optimistic that breast cancer care will look different over the next few years and that vaccines for cancer will move away from treating advanced disease to making a difference at earlier stages. Vonderheide believes that the era of using cancer vaccines with hope in a patient who has already been treated with everything is over. In 10 years, cancer is going to be about prevention and survival, and I believe vaccines will play a part in that.

Lynch is hoping that will happen. 25 years after her aunt was diagnosed with breast cancer, the disease recurred and spread to the brain. Lynch achieved her goal of surviving at least that long without cancer. She wants to be a 26 year survivor. I made it and I want to keep making it.

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