10 November 2022

DNA vaccine against cancer

Researchers from the University of Washington School of Medicine in Seattle in a clinical study showed the safety of a vaccine against breast cancer. Since this study was not randomized, its results should be considered preliminary, and now the vaccine will be evaluated in a larger randomized clinical trial.

The vaccine being tested targets the epidermal growth factor receptor 2 (HER2). It is a membrane protein present on the surface of many cells, but in 30% of breast cancer cases it is produced hundreds of times more than in normal cells. HER2-positive breast cancer is generally more aggressive and more likely to recur after treatment, but excess HER2 often triggers a cytotoxic immune response that reduces the risk of recurrence and increases overall survival.

An experimental vaccine stimulates this kind of reaction, but unlike protein vaccines, which usually contain the protein itself or a fragment of it, to which the immune system must respond, it carries DNA instructions for the target protein HER2.

After injection, the cells absorb the DNA of the vaccine and begin to produce HER2 encoded in it. The immune system, when confronted with this protein, triggers a powerful cytotoxic reaction.

The study involved 66 women with metastatic stage of breast cancer. All of them received standard therapy and either achieved stable remission, or a tumor remained in the bone, which tends to slow growth.

The study participants were divided into three groups: low (10 mcg), medium (100 mcg) and high (500 mcg) doses. Each group received three injections of the vaccine. The participants were also given granulocyte-macrophage colony stimulating factor (GM-CSF), an immunostimulating drug that promotes cytotoxic immunity.

Then the participants were followed from 3 to 13 years (on average, about 10 years). Long-term follow-up was important because HER2 is also present in healthy cells, and the researchers wanted to make sure that vaccination over time would not trigger an autoimmune response against healthy tissues carrying HER2.

The results showed that the vaccine was safe. The most common side effects of vaccination were general reactions: redness and local swelling at the injection site, short-term fever, chills and flu-like symptoms.

The vaccine successfully triggered the desired cytotoxic immune response, most pronounced in the group receiving the average dose, and slowed down the progression of the tumor. According to statistics, approximately half of patients with similar stages of breast cancer die within 5 years after treatment; study participants have been under observation for an average of ten years, and 80% of them are still alive.

Article by M.Disis et al. Safety and Outcomes of a Plasmid DNA Vaccine Encoding the ERBB2 Intracellular Domain in Patients With Advanced-Stage ERBB2-Positive Breast Cancer is published in JAMA Oncology.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Washington School of Medicine: Breast cancer vaccine safely generates anti-tumor immunity.


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