New vaccine shows promise in treating aggressive form of breast cancer

By Stephen Beech

Breast cancer patients have been given fresh hope after a new vaccine showed "promise" in treating an aggressive form of the disease.

The results came in a clinical trial involving American patients with triple-negative breast cancer who received an experimental jab designed to prevent the recurrence of tumors.

The trial, using a therapy designed by researchers at Washington University School of Medicine in St. Louis, is the first to report results for the type of vaccine - known as a neoantigen DNA vaccine - for breast cancer patients.

The findings, published in the journal Genome Medicine, showed the vaccine to be "well-tolerated" and to stimulate the immune system.

The trial involved 18 patients diagnosed with triple-negative breast cancer that was not "metastatic" - meaning it had not spread to other organs.

Each patient received the standard of care and three doses of a personalized vaccine tailored to home in on key mutations in their specific tumor and train immune cells to recognize and attack any cells bearing the mutations.

Following treatment, 14 of the 18 patients showed immune responses to the vaccine and, after three years, 16 patients remained cancer-free.

While the early-stage trial was designed to evaluate the safety of the vaccine and did not include a control group to determine efficiency, the research team analyzed historical data from patients with triple-negative breast cancer treated with the standard of care only.

In that group, on average, only about half of patients remained cancer-free three years after treatment.

Study senior author Professor William Gillanders, of Washington University School of Medicine, said: “These results were better than we expected.

“Obviously, it’s not a perfect comparison, and we acknowledge the limitations of this type of analysis, but we are continuing to pursue this vaccine strategy and have ongoing randomized controlled trials that do make a direct comparison between the standard of care plus a vaccine, versus standard of care alone.

"We are encouraged by what we’re seeing with these patients so far.”

Triple-negative breast cancer is an aggressive tumor type that grows even in the absence of the hormonal fuel that drives the growth of other types of breast cancer.

It currently has no targeted therapies and is usually treated with traditional approaches including surgery, chemotherapy and radiation therapy.

For the trial, patients with triple-negative breast cancer who still had evidence of a tumor remaining after a first round of chemotherapy were eligible to participate.

Researchers say such patients are at "high risk" of cancer recurrence even after the remaining tumor is surgically removed.

After surgery, the team analyzed and compared the tumor tissue with the same patient’s healthy tissue to find unique genetic mutations in the cancer cells.

Such mutations in a patient’s cancer cells alter the proteins only in the tumor, making it possible to train the immune system to go after the altered proteins and leave healthy tissues alone.

Using software they designed, the researchers selected altered proteins - called neoantigens - that were made by the patient’s tumors and that were identified as most likely to trigger a strong immune response.

On average, each patient’s vaccine contained 11 neoantigens - ranging from a minimum of four to a maximum of 20 - specific to their tumor.

A paper published simultaneously in the same journal describes the software tools the team developed.

One of their goals is to make computational resources widely accessible to cancer researchers and doctors worldwide.

Professor Malachi Griffith, who co-led the software development, said: “We hope to promote the use of this software for the design of cancer vaccines.

“These are complex algorithms, but in general, the software takes in a list of mutations and interprets them in the context of their potential to be good neoantigen candidates.

"The tools rank the possible neoantigens based on our current knowledge of what matters in stimulating the immune system to attack cancer cells.

"These software tools were developed with support from the National Cancer Institute, and they have an open license that makes them broadly available for both academic and commercial uses.”

Several studies of cancer vaccines developed at Washington University School of Medicine are currently ongoing.

In some of the trials for breast cancer patients, personalized vaccines are being investigated in combination with immunotherapies called checkpoint inhibitors that boost the action of T cells.

Gillanders said: “We are excited about the promise of these neoantigen vaccines.”

He added: “We are hopeful that we will be able to bring more and more of this type of vaccine technology to our patients and help improve treatment outcomes in patients with aggressive cancers.”