A new paper in the journal JAMA Oncology has reported the results of a decade-long Phase 1 human trial testing an experimental breast cancer vaccine. The novel treatment was found to be "very safe" and a larger Phase 2 trial is now underway testing efficacy.
Up to 30% of breast cancers involve the overproduction of a protein called human epidermal growth factor receptor 2 (HER2). These HER2-positive cancers are often more aggressive than other types of breast cancer, growing faster and being more likely to reoccur.
For the last couple of decades one of the more effective clinical treatments for this type of breast cancer has been a monoclonal antibody therapy designed to block the activity of HER2 on tumor cells. However, researchers have long been working on vaccines that can train the immune system to target these HER2-positive tumor cells.
These kinds of cancer vaccines are not designed to be preventative vaccines that stop cancers from appearing in the first place. Instead, these are known as therapeutic vaccines, given to patients after they are diagnosed with a cancer in the hopes they help the immune system better seek and destroy certain tumors.
In this instance researchers are working with what is called a DNA vaccine. These vaccines deliver DNA blueprints for the production of certain proteins into the nucleus of a cell. That protein is then produced by the cell, triggering an immune response. The vaccine being tested prompts cells to produce a specific fragment of the HER2 protein.
This Phase 1 trial began 20 years ago, slowly enrolling 66 patients with advanced HER2-positive breast cancer. Three different dose levels were tested, with the primary goal of the trial to evaluate the long-term safety of the vaccine. Because HER2 proteins can be found on other cell types in the body, the researchers planned a 10-year follow-up for each participant to make sure there were no lingering problems of immune activity against healthy tissue.
“The results showed that the vaccine was very safe,” said lead author on the new study Mary Disis. “In fact, the most common side effects that we saw in about half the patients were very similar to what you see with COVID vaccines: redness and swelling at the injection site and maybe some fever, chills and flu-like symptoms.”
The trial was not geared to evaluate how effective the experimental vaccine is at treating breast cancer. But Disis did point out promising early signs of efficacy, with 80% of the treated trial participants surviving the full 10-year follow-up. Disis said only around 50% of patients with advanced HER2 breast cancer would generally be expected to survive more than five years, so it's likely the vaccine is working.
A Phase 2 trial is currently underway, testing the vaccine's efficacy in a larger cohort of HER2-positive patients. That trial kicked off a few years ago and only has a two-year follow-up period. So preliminary results could start coming within the next couple of years.
“If the results of the new randomized-controlled Phase 2 trial of the vaccine are positive, it will be a strong signal for us to rapidly move forward to a definitive phase III trial,” Disis added. “I have high hopes that we’re close to having a vaccine that can effectively treat patients with breast cancer.”
The new study was published in JAMA Oncology.
Source: UW Medicine