Scientists at the University of Washington School of Medicine in Seattle (United States) have carried out a phase I clinical trial to test the safety and efficacy of a new experimental vaccine to combat breast cancer. The results of the study have been published in JAMA Oncology and show that the drug has generated a strong immune response to a key tumor protein: the HER2 protein. According to the results, this vaccine could be used in the treatment of various types of breast cancer.
“Because this was not a randomized clinical trial, the results should be considered preliminary, but the findings are promising enough that the vaccine is now being evaluated in a larger randomized clinical trial,” said Dr. Mary ‘Nora. ‘ L. Disis, UW professor of medicine, Division of Medical Oncology, director of the Cancer Vaccine Institute, and lead author.
The study aimed to assess the safety of a vaccine that targets a protein called human epidermal growth factor receptor 2 (HER2) and to see if it generated an immune response to that protein. HER2 is found on the surface of many cells, but up to 30% of breast cancers produce up to 100 times more HER2 than healthy cells.
“The results showed that the vaccine was very safe, I have high hopes that we are close to having a vaccine that can effectively treat breast cancer patients”
‘HER2-positive’ cancers tend to be more aggressive and more likely to recur after treatment, but excessive HER2 production also triggers an immune reaction that may be beneficial, as HER2-positive breast cancer patients generate a type of an immune response called cytotoxic (or cell-killing) immunity that reduces the chance that the cancer will come back after treatment and leads to longer overall survival than those who do not develop such an immune response.
The vaccine stimulated the desired cytotoxic immune response
To stimulate this type of response, Disis and his colleagues created a DNA vaccine that contained the DNA instructions for a part of HER2 – the target protein – that is usually found inside the cell. This intracellular portion is known to elicit stronger cytotoxic immune responses. The study enrolled 66 women with metastatic cancer who had undergone a standard course of therapy and achieved a complete remission, or had only a tumor in the bone, which is usually slow-growing.
These patients were divided into three groups and three injections were administered to each of the participants. One group received three low-dose injections (10 mcg) of the vaccine, another group received three injections with an intermediate dose of 100 mcg, and another group three high-dose injections (500 mcg). They also received the immunostimulatory drug granulocyte-macrophage colony-stimulating factor (GM-CSF), which promotes cytotoxic immunity.
The researchers followed the participants for between three and 13 years, with an average follow-up of almost 10 years. This long follow-up was necessary because HER2 is found in many other cell types and they wanted to make sure that over time the vaccination did not trigger an autoimmune response against other healthy tissues that carry HER2.
“The results showed that the vaccine was very safe,” said Disis. “In fact, the most common side effects we saw in about half of the patients were very similar to those seen with COVID vaccines: redness and swelling at the injection site and maybe some fever, chills. and flu-like symptoms.
The vaccine was successful in stimulating the desired cytotoxic immune response without triggering serious side effects, with the strongest immune response occurring in patients receiving the medium dose. “We have followed these women for ten years and 80% of them are still alive,” Disis highlighted, concluding: “If the results of the new randomized controlled phase II trial of the vaccine are positive, it will be a strong signal for that we move quickly to a definitive phase III trial.” “I am very hopeful that we are close to having a vaccine that can effectively treat breast cancer patients.”
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