Scientists Developing Vaccine to Prevent Deadly Form of Breast Cancer

A new trial of the experimental vaccine is underway. One day it may offer immunity to those at risk.

A patient in a blue gown faces a mammogram machine, while a healthcare provider stands by.

A rare and deadly form of breast cancer may one day be a vaccine-preventable disease. Researchers at the Cleveland Clinic are testing an innovative vaccine that could stop a deadly form of breast cancer just as it starts. They’ve launched an early-phase trial of an experimental vaccine against triple-negative breast cancer, an uncommon type of breast cancer that is hard to treat and often lethal.

The vaccine is designed to teach the immune system to spot and destroy a new triple-negative tumor just as it begins forming in the breast.

“What we’re trying to do is what we call primary prevention,” says Vincent Tuohy, Ph.D., the primary inventor of the vaccine and staff immunologist at Cleveland Clinic’s Lerner Research Institute. “We’re trying to prevent the emergence of the tumor and prevent it from ever happening.”

If the vaccine succeeds, this type of breast cancer might one day be preventable, in much the same way that the human papilloma virus (HPV) vaccine can prevent cervical cancer and childhood vaccines can prevent infectious diseases, like measles and polio.

Who is involved in the study?

Funded by the Department of Defense, the Phase 1 vaccine trial will enroll up to 24 adults who have been successfully treated for triple-negative breast cancer within the past 3 years, but who are at high risk for the tumors to come back. The participants will receive three doses of the vaccine two weeks apart. After receiving the vaccine, they will be monitored for side effects. Blood tests will also reveal how their immune systems respond.

“Every day I see the needs of women who have triple negative breast cancer, yet we don't currently have suitable advanced treatment options for them. Our ultimate goal is to offer a proactive approach to help women before they reach that point,” says principal investigator G. Thomas Budd, MD, of Cleveland Clinic’s Taussig Cancer Institute. “Our hope for the future…is to make available a vaccine that prevents triple-negative breast cancer in women at high genetic risk for this form of breast cancer who are otherwise healthy and cancer-free.”

“For women at high risk of breast cancer, I think this would be of incredible benefit,” adds Pamela Munster, MD, a medical oncologist, expert in early cancer prevention, and professor of medicine at the University of California, San Francisco, who is not involved with the trial.

Why this form of breast cancer is so tough to treat

Only about 10 to 15 percent of all breast cancers are triple-negative, but these cancers account for more deaths than other breast cancer types. It’s also more likely than other breast cancers to come back after successful treatment. Black and Hispanic people and those who have a mutation in the breast-cancer gene BRCA1 are disproportionately affected. Many who learn they have such a risky mutation opt for a mastectomy to cut the chances that a cancer will develop. (People of any gender can develop breast cancer.)

“Triple negative” refers to the fact that this type of breast cancer is missing three key vulnerabilities. Most breast cancers’ cell surfaces sport receptors, like docking stations, that connect with certain hormones—estrogen, progesterone, or both—or with a protein called HER2. If the cell has any of those three receptors, the corresponding hormone or protein is fueling the cancer’s growth. Those fuel supplies can be cut off. Drugs designed to block that hormone or interfere with the HER2 receptor can help choke off those cancers’ growth.

Unfortunately, triple-negative cancers lack all three receptors, so they remain untouched by those targeted drugs. Instead, people with triple-negative breast cancers are treated with chemotherapy and radiation—classic cancer treatments that target all fast-growing cells, healthy and cancerous, indiscriminately. This blanket approach comes with side effects and often does not cure the cancer.

How the vaccine works

The experimental breast cancer vaccine zeroes in on a protein that breast-cancer cells make that is lacking in the normal breast cells of non-pregnant, non-lactating people. Called alpha-lactalbumin, this protein is created by the healthy breast during late pregnancy and breastfeeding only. It doesn’t reappear except with breast cancers, which resurrect and pump out alpha-lactalbumin protein during early growth.

“What’s different about their vaccine, and what’s clever, is lactalbumin is a protein or a target that’s expressed in lactating women. It is not expressed on breast cells if you’re not lactating,” Dr. Munster notes. “The goal with this is they will capture a target that’s only expressed in breast cancer.”

This explains why people who are lactating are not eligible to participate in the vaccine trial. It teaches the immune system to detect the out-of-place alpha-lactalbumin and to destroy cancer cells that are creating it. The strategy has worked to prevent breast cancers in mice, as well as to control the growth of those that already exist, Tuohy’s team reported in a May 2010 article in Nature Medicine.

“The [immune] cells, those angry lymphocytes that are out there to kill something—it’s like a guided missile, but you actually have to have a target,” Munster explains.

The vaccine is made by Anixa Biosciences, Inc., to which Cleveland Clinic has exclusively licensed the technology. Tuohy will receive part of Cleveland Clinic’s revenues for the vaccine and he also holds personal equity in the company.

Immunotherapy for cancer: a science in its infancy

Anixa’s investigational vaccine is an example of immunotherapy, a group of cancer treatment approaches that harness the immune system.

You may think of the immune system’s main job as fighting off harmful bacteria and viruses. But it is also believed to suppress some early cancers.

When mutations in a cell’s DNA lead to its dividing over and over again, the result can be cancer. But in healthy individuals, immune cells are thought to be able to spot and stop many of those runaway events, controlling or even eliminating tumor growth. This process, called immune surveillance, is why a healthy immune system is a key part of cancer prevention.

But some cancers are wily, evading immune recognition and destruction. In such cases, immunotherapy tactics can sometimes help guide the immune system’s “attention” to the cancer or otherwise help unleash its innate ability to destroy renegade cells.

“The immune system is capable of keeping us healthy. That’s what it does. That’s its job. That’s what it’s designed to do, and we just have to tap into it,” Tuohy says. “A vaccine is just a program, the way word processing is a program for your operating system on your computer. So it’s just a program that tells the immune system what to do.”

A world where cancers are vaccine-preventable?

The triple-negative vaccine, if it works, would not be the first to treat or prevent cancer. There is already a vaccine to prevent infection by several dangerous strains of HPV—the virus responsible for genital warts. Because those particular strains are responsible for most cervical cancers and many cancers of the throat and anus, the HPV vaccine indirectly but effectively prevents those cancers. In a similar way, vaccination against the hepatitis B virus can prevent liver cancer.

Cancer vaccines also exist to treat bladder cancers, advanced prostate cancer, and recurrent melanoma. But their success is often only modest. Treating pre-existing tumors does not work nearly as well as preventing tumors from forming in the first place, according to Tuohy.

“I’m very excited about vaccines, of course, with a very sobering dose of realism that vaccines have not been very successful in the cancer world,” Munster cautions.

Developing vaccines to treat cancer is very difficult. For one thing, cancers arise from a person’s own cells, which the immune system may not easily recognize as harmful the way it does a virus from the outside world. Cancer calls can also suppress or escape the immune response. And cancers often arise in older people, and the immune system tends to weaken with age.

Tumors may grow too large for immune cells to fully reach and penetrate. That’s one reason the researchers at Cleveland Clinic and elsewhere are focused on vaccines that could prevent cancer outright, or at least stop it very early.

In addition, Munster says, “the immune system is very fickle.” It can be hard to predict how it will respond to being stimulated, she explains. And if it overreacts, causing a massive inflammatory response and unwanted side effects, it can be hard to dial down. Dangerous and even lethal immune reactions to other types of immunotherapy have occurred.

“When you engage the immune system all of a sudden, you need to have a way to stop your response, and that’s not often trivial,” she says.

Despite these challenges, around the world, studies are also underway to test vaccines for bladder, blood, brain, cervical, colorectal, kidney, lung, skin, and pancreatic cancers. Other breast cancer vaccine trials have begun as well, most of them aimed at treating existing tumors or preventing tumors from recurring.

Tuohy’s team is also working on vaccinations to prevent ovarian cancer and cancers of the lining of the uterus.

If the current triple-negative breast cancer vaccine trial is successful—that is, if the vaccine results in an immune response and if side effects are tolerable—then the next step will be to study its use prior to breast removal in cancer-free people who have high-risk genetic mutations and are planning on a preventative mastectomy to reduce their odds of developing the disease.

Clinical trials will take years, and the vaccine’s success is not certain. But an effective, FDA-approved vaccine might allow many such people at high risk to avoid this preemptive surgery on otherwise healthy breast tissue. 

Any time you start on a new approach, it’s exciting. But also realize it’s going to take years to get to our final goal, and there are potential hurdles all along the way, as there have been hurdles just to get to this point,” Dr. Budd says. “I’m optimistic, though, that we can overcome those hurdles and help women who are at risk for breast cancer.”

Article sources open article sources

Cleveland Clinic. “Cleveland Clinic Launches First-of-its-Kind Preventive Breast Cancer Vaccine Study.” Oct. 26, 2021. “Triple-Negative Breast Cancer.” Aug. 28, 2021.
Harvard Health Publishing. “Angelina Jolie’s prophylactic mastectomy a difficult decision.” May 15, 2013. “Media Coverage of Celebrities’ Breast Cancer Treatment May Be Contributing to Rise in Double Mastectomies.” May 3, 2016. “Molecular Subtypes of Breast Cancer.” Apr. 7, 2021. “Male Breast Cancer Is Different in Terms of Biology and Outcomes.” Dec. 17, 2014.
Tuohy VK, Jaini R, Johnson JM, et al. Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer. Cancers (Basel). 2016;8(6):56. Published 2016 Jun 16. doi:10.3390/cancers8060056.
Jaini R, Kesaraju P, Johnson JM, Altuntas CZ, Jane-Wit D, Tuohy VK. An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Nat Med. 2010;16(7):799-803.
Tuohy VK. A prophylactic vaccine for breast cancer? Why not?. Breast Cancer Res. 2010;12(6):405. doi:10.1186/bcr2775
T Cells Prevent the Development of Spontaneous B-cell Lymphomas. Cancer Discov. Apr. 1, 2014.
Cancer Treatment Centers of America. “Vaccines.”
The University of Texas MD Anderson Cancer Center. “The cancer prevention vaccine.” Fall 2014. What Are Cancer Vaccines? Aug. 2020.
Breast Cancer Research Foundation. “Breast Cancer Vaccines Explained.” June 15, 2021. “Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Triple-Negative Breast Cancer.” Posted Dec. 19, 2020.
American Cancer Society. “Triple-negative Breast Cancer.” Jan. 27, 2021.

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