World’s first breast cancer vaccine candidate enters human trials

• Human trials are underway for a vaccine against the most aggressive and deadly form of breast cancer.
• The phase 1 trial will include early stage triple-negative breast cancer survivors who are at high risk for recurrence.
• The vaccine targets a protein called α-lactalbumin and alerts the immune system to halt tumor growth.
• Although it is too early to call this finding a breakthrough, if the trial progresses, it could possibly inspire similar shots for other cancers, as well.

In what could be a world first, researchers are now testing a vaccine that aims to prevent a particularly aggressive form of breast cancer in human trials in the United States.

They have designed the vaccine to prevent triple-negative breast cancer (TNBC) — which is currently only preventable with a mastectomy — in those at high risk. Ideally, it would also become a booster for people who have already survived this type of cancer.

The hormones estrogen and progesterone do not fuel TNBC, and neither does an excess of the human epidermal growth factor receptor 2 (HER2) protein that helps cells grow.

This type of cancer is fast-spreading and more difficult to treat as it does not respond to hormonal medicines, such as tamoxifen, or targeted drug therapies, such as palbociclib (Ibrance).

TNBC accounts for about 10–15% of all breast cancers. Between 2012 and 2016, it had an 8–16% lower survival rate in the U.S. than hormone-receptor types.

What will the trial look like?

Following clearance from the Food and Drug Administration (FDA) for the testing of the experimental new drug, the Cleveland Clinic and partner Anixa Biosciences, Inc. launched the study in early October to determine the correct dosage for the vaccine.

Initially, the trial will include 18–24 participants, all of whom have received treatment for early stage TNBC in the past 3 years. Although doctors have declared each person tumor-free, they are at high risk for recurrence.

The scientists running the trial will administer the vaccine as three shots with 2 weeks between each dose. They will closely monitor the participants for side effects and immune response.

The trial will include a larger number of participants, who will be in good health, if the dosage proves to be safe and effective.

The study has funding from the Department of Defense, and the team expects to complete it in September 2022.

A new way to control breast cancer

The vaccine targets α-lactalbumin, a protein that plays an important role in milk production. Under normal circumstances, the body only produces it during late pregnancy and lactation. However, research has found that the protein is overexpressed in emerging tumors.

By arming the immune system to target α-lactalbumin, the body will be able to fight off tumor cells that produce the protein in the future. It will also leave healthy breast tissue alone, limiting damage to the body.

Vincent Tuohy, Ph.D., the primary inventor of the vaccine and staff immunologist at Cleveland Clinic’s Lerner Research Institute, led the team of researchers, who vaccinated female mice against the α-lactalbumin protein and found that it caused no autoimmune inflammation.

“This indicated to us that we could vaccinate against α-lactalbumin without inducing any tissue damage. When we found that α-lactalbumin vaccination inhibited the appearance of breast tumors in mice, we were thrilled,” Dr. Tuohy told Medical News Today.

The team got the same results from several other animal models of breast cancer, which was necessary for the vaccine to advance to human clinical trials.

“I found it very interesting and innovative, [as the vaccine] targeted a particular protein that they’re calling a ‘retired protein,’ which is specifically found in a certain time period in a woman. [T]hey found that that protein is also highly prevalent in malignant breast tissue,” said Dr. Bhavana Pathak, a medical oncologist and hematologist at MemorialCare Cancer Institute at Orange Coast Medical Center in California.

She said that it was “very promising and fortuitous” that the researchers were able to prevent the development of breast tumors and then also stop the growth of existing tumors with the vaccine in animal models.

What makes the vaccine revolutionary in the area is that it emulates the strategy of childhood vaccines by aiming to prevent and eradicate the disease. Therapies so far have focused on treating breast cancer after the disease has developed.

“We have known since 1982 that providing immunity prior to the development of tumors can prevent the tumors from growing. Yet most cancer vaccination studies have focused on using vaccines as treatment vehicles rather than for prophylaxis.”

– Prof. Vincent Tuohy

Emphasizing that the childhood vaccination program is built on prophylaxis, which refers to preventing disease rather than treating it afterward, Dr. Tuohy explained the reasoning behind applying the same strategy to breast cancer:

“We don’t wait to get polio or measles and then vaccinate. We provide the immunity preemptively,” he told MNT.

The next step would be to offer the vaccine to healthy people at high risk for breast cancer, including those with BRCA1 gene mutations.

“In this way, the immunity to cancer can be induced preemptively without causing any autoimmune complications, and when the tumor emerges, it is killed before it has a chance to grow into a mature entity that is very difficult to treat,” he said.

The challenges of being ‘a first’

Dr. Tuohy pointed out that these are early phase 1 safety and dosage trials and that researchers will only be able to determine efficacy in phases 2 and 3.

Speaking with MNT, Dr. Charles Shapiro, professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, NY, underscored that there is still a long way to go.

“This phase 1 study is a dose-finding study with an end point of assessing whether there is an immune response to the vaccine. Phase 1 trials are necessary as they often represent first-in-human experience after some treatment is promising in the preclinical setting. By definition, phase 1 is too small to draw any conclusions about the anti-cancer effects,” he said.

However, he underlined that every treatment that scientists now deem effective was once in a phase 1 trial setting and that mounting such a trial was an impressive feat.

Apart from being quite a small trial, the obvious challenge will be the adverse events, said Dr. Pathak.

Hence, the patient population will be a key component of the trial, noted Dr. Shapiro.

“If entry criteria include heavily pre-treated stage 4 patients, there is some uncertainty whether the immune responses to the vaccine will be robust,” he said.

Dr. Tuohy acknowledged that challenges lie ahead:

“Several obstacles still remain, including adverse events that our vaccine may potentially cause — particularly because it is completely novel, containing a vaccine target and a vaccine adjuvant that have never been used in human clinical trials.”

Applying such preventive strategies to cancers are also trickier because the researchers have to choose the target appropriately, said Dr. Pathak.

“Another concern I have is that, ultimately, this is a very specific target during a specific time period. You have to be ‘older,’ targeting premenopausal patients but who have stopped lactating. My hope is that eventually, we’ll find another target in women who are still lactating and use it earlier,” she told MNT.

Inspiring new strategies to fight other cancers

Dr. Pathak stressed that although vaccine studies have been underway for many years, the silver lining of the COVID-19 pandemic has been their application to cancer, which is “extremely exciting.”

“I think we’re in the golden era of immune-mediated therapy, and in almost every area of oncology, we’re using or finding novel uses for immunotherapy and also therapies like vaccines that activate the immune system to both prevent and treat disease. That’s the beauty of translational research where it’s like bench to bedside,” she said.

“We’ve done this with other types of cancers; more preventively with cervical cancer and the human papillomavirus vaccine, and with hepatocellular carcinoma and the hepatitis B vaccine. Those are truly remarkable.”

– Dr. Bhavana Pathak

Dr. Pathak expressed her hope that in the near future, researchers can find other tissue-specific targets in other diseases, such as prostate, lung, or ovarian cancers — which are common and potentially deadly cancers — to transform the field of oncology.

And it seems that Dr. Tuohy and his team are already working on a vaccine to prevent epithelial ovarian carcinoma (EOC), the most common form of ovarian cancer.

“EOC is the most lethal of all gynecologic malignancies, killing 53% of women within 5 years of diagnosis. This vaccine is undergoing development in collaboration with the National Cancer Institute’s PREVENT Program, and we hope to start clinical trials within the coming few years,” he said.

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