Researchers at the University of Washington School of Medicine in Seattle have tested an experimental breast cancer vaccine in phase 1 trials. The vaccine in question targets the protein HER2, a transmembrane receptor involved in the regulation of cell proliferation, which is overexpressed in most cases. mammary cancer. The vaccine elicited a strong immune response against this protein, suggesting that it may be effective in treating various types of breast cancer.
The HER2 receptor is a protein naturally present in the cells of the body. But in 30% of breast cancer cases, this protein is overexpressed (up to 100 times more than normal) - this is called “HER2-positive” or HER2+ cancer. This overproduction promotes the growth of cancer cells and the appearance of metastases, so this type of cancer is especially aggressive and the risk of recurrence is high.
However, overproduction of HER2 can also trigger an immune response in some patients that can be beneficial, a cytotoxic response aimed at killing unhealthy cells that carry this protein. After such an immune response, the risk of recurrence is much lower. Dr. Mary Disis, an expert in breast and ovarian cancer immunology and immunotherapy and director of the Cancer Vaccine Institute, and her team have found a way to stimulate this immune response with a DNA vaccine.
DNA vaccine with HER2 protein
As the name suggests, this vaccine contains the DNA of the HER2 protein, the genetic instructions needed to create it. More specifically, it contains the DNA that codes for the part of the HER2 protein that normally stays inside cells. This intracellular portion is known to elicit a stronger cytotoxic immune response.
After injection, this DNA is taken up by the cells at the injection site; the latter will then produce the intracellular portion of HER2 and thus generate the expected immune response. This vaccine candidate was tested in 66 women with metastatic cancer in a Phase 1 non-randomized safety study conducted from 2001 to 2010.
All participants had previously received standard treatment (based on trastuzumab, a monoclonal antibody directed against HER2); at the time of the study, they were in complete remission or still had bone tumors that tended to grow slowly.
These women were divided into three groups: one group received three injections of a low dose (10 mcg) of the vaccine, one group received three injections of an intermediate dose of 100 mcg, and the last group received three injections of a high dose, i.e. 500 mcg. They also received adjuvant supplementation with granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycoprotein naturally produced by several cell types that promotes cytotoxic immunity.
Participants were then followed for 3 to 13 years (median follow-up was almost 10 years). This long-term follow-up was necessary to ensure that the vaccine would not trigger an autoimmune response over time against other healthy tissues that carry the HER2 protein.
Towards a “universal” cancer vaccine?
The vaccine proved to be safe and effective: it induced the expected cytotoxic immune response (i.e., the production of “killer” T cells) without serious side effects. “The most common side effects we saw in about half of the patients were very similar to those you see with COVID vaccines: redness and swelling at the injection site and possibly some fever, chills and flu-like symptoms,” Dr. Disis. .
The strongest immune response occurred in patients who received an intermediate dose of vaccine, i.e. 100 μg of HER2 plasmid DNA. This trial was not designed to evaluate the ability of a vaccine to stop or slow the progression of cancer; however, the team did note promising positive effects: half of the participants had a five-year life expectancy after treatment, but after a median follow-up of ten years, 80% of study participants still needed help.
These are only preliminary results, but they are encouraging enough as the vaccine is currently undergoing a large randomized clinical trial. “I hope that we are on the threshold of creating a vaccine that can effectively treat patients with breast cancer,” said the expert. Breast cancer has become the most frequently diagnosed cancer in the world, with an estimated 2.3 million new cases in 2020.
Note that vaccines already exist to prevent certain types of cancer. They target viruses: the hepatitis B virus, which can cause liver cancer, and the human papillomavirus (HPV), which causes cervical and some other cancers. But most cancers are not caused by viruses, hence the interest in using vaccines containing fragments of proteins known to be tumor antigens.
Because sequencing has shown that relatively few genes are involved in most cancers, a limited number of antigens could lead to broad protection against several cancers. “We are far from a universal vaccine to prevent cancer. But that may be in the distant future. It’s a step-by-step approach,” says Shizuko Sei, an oncologist at the National Cancer Institute’s Cancer Prevention Unit.