An experimental breast cancer vaccine has been shown to safely generate a strong immune response against a key tumor protein in a small study of more than 70 women with metastatic breast cancer. The results, published in the journal JAMA Oncology, show that 80% of treated women were still alive ten years after receiving the vaccinefive years more than what is achieved with existing therapies.
However, “because this is not a randomized clinical trial, the results should be considered preliminary, but they are promising enough that the vaccine is now being evaluated in a larger randomized clinical trial,” says lead author Mary L. Disis, from the University of Washington School of Medicine in Seattle (USA).
Breast cancer is, in general, a tumor with a good prognosis, but some subtypes are more aggressive. One of the variants with the highest mortality rate is HER2 positive, since the alteration of this gene causes signals to be transmitted to tumor cells so that they grow faster than normal, accelerating the progression of the disease. This implies a greater risk of metastasis and of the cancer spreading to other different organs.
The phase I trial was designed 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 the protein.
HER2 is found on the surface of many cells, but it is known that in up to 30% of breast cancers, up to 100 times more HER2 is produced than in normal cells. These HER2-positive tumors tend to be more aggressive and more likely to come back after treatment, but the overproduction of HER2 also triggers an immune reaction that can be beneficial.
In 30% of breast cancers, an excess of HER2 is produced up to a hundred times more than in normal cells
Specifically, patients with HER2-positive breast cancer who mount a type of immune response called cytotoxic (or cell-killing) immunity are less likely to have their cancer come back after treatment and have longer overall survival than those who do not. this immune response.
To stimulate this type of response, the researchers made a DNA vaccine.
Unlike protein vaccines, which typically contain a protein or part of a protein that you want the immune system to target, DNA vaccines contain the DNA instructions for the target protein.
Once injected, this DNA is taken up by cells at the injection site, which then begin to produce the protein encoded in the vaccine’s DNA instructions. The cells will then present the protein to the immune system, a process that is likely to generate a strong cytotoxic immune response.
The vaccine used in this trial contained the DNA instructions for a part of HER2 that is usually found inside the cell.. This intracellular portion is known to elicit stronger cytotoxic immune responses.
In all, 76 women who had metastatic cancer were enrolled in the study. All of them had completed a standard course of therapy and had either achieved a complete remission or had only a tumor left in the bone, which tends to grow slowly.
Study participants were divided into three groups, with each participant receiving three injections: one group received three low-dose injections (10 mcg); another an intermediate dose of 100 mcg and the third 3 injections of high dose, 500 mcg.
They also received the immunostimulatory drug granulocyte-macrophage colony-stimulating factor (GM-CSF), which promotes cytotoxic immunity.
The team followed the participants for three to 13 years (average follow-up was nearly 10 years). Long-term follow-up is important because HER2 is found on many other cell types. The researchers wanted to make sure that vaccination did not trigger an autoimmune response against other healthy tissues that carry HER2 over time..
“The results showed that the vaccine was very safe,” says Disis. In fact, the most common side effects seen in about half of the patients were very similar to those seen with Covid vaccines: redness and swelling at the injection site and perhaps some fever, chills, and symptoms. flu-like.
The participants have done much better than would be expected in patients with similar stages of breast cancer
The vaccine also successfully stimulated the desired cytotoxic immune response without triggering serious side effects. and the strongest immune response appeared in patients who received the medium dose.
Although the study was not designed to see if the vaccine could slow or prevent cancer progression, the participants have fared much better than would be expected in patients with similar stages of breast cancer, about half of whom He would die within 5 years of treatment.
“We have followed these women for ten years and 80% of them are still alive,” Disis points out, adding that if the results of the new randomized controlled phase II trial of the vaccine are positive, it will be a strong signal to start a definitive phase III trial. “I have high hopes that we are close to a vaccine that can effectively treat breast cancer patients.”