A vaccine to help chemotherapy
Personalized vaccine has increased the effectiveness of ovarian cancer treatment
Daria Spasskaya, N+1
Researchers from the University of Pennsylvania have shown the safety and presumed effectiveness of cancer vaccines based on their own dendritic cells of patients with ovarian cancer. Women who received the vaccine in addition to standard chemotherapy had a higher chance of surviving for two years. The results of a pilot trial on patients were published by scientists in Science Translational Medicine (Tanyi et al., Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer).
An image of a tumor in one of the patients, obtained using computed tomography, before and during treatment. Drawings from the article in Sci. Transl. Med.
The standard treatment for ovarian cancer in the last stages is surgical removal of the tumor and supportive chemotherapy, which prevents the remaining tumor cells from multiplying. Despite these measures, the tumor grows again in a significant part of the patients. In order for the patient's own immunity to start fighting cancer cells on its own and "help" doctors to destroy the malignant formation, scientists are developing various methods of immunotherapy, one of which is anti–cancer vaccines based on dendritic cells.
Dendritic cells are immune cells whose task is to find a foreign antigen (an unfamiliar protein), eat it and put it on its surface. Then the antigen-presenting cells are sent to the lymph nodes, where T-lymphocytes are "trained" to recognize foreign proteins and destroy the cells on which these antigens are located. Dendritic cells are quite easy to obtain from non-specialized leukocytes in vitro. If such cells in a test tube are "fed" with the necessary antigens (for example, cancer), and then injected into the patient's body, the cells will train the patient's own lymphocytes to fight cancer cells.
This is the approach used by scientists from the Ovarian Cancer Research Center at the Perelman School of Medicine at the University of Pennsylvania (USA). To create personalized vaccines against ovarian cancer, white blood cells were taken from patients, turned into dendritic cells and incubated with a specific patient's tumor extract. In the process of tumor growth, cells mutate and they have new antigens that were not present in the body before, so incubation with tumor extract should have led to the appearance of "advanced" dendritic cells that would know about the modification of the tumor and could inform the lymphocytes about it. After the preparation of the vaccine, dendritic cells were injected into the lymph nodes of the patients.
The scheme of the experiment for the preparation of the vaccine.
DC – dendritic cells.
25 patients with recurrent ovarian cancer of the third and fourth stages took part in the pilot trial of vaccines. Five of them received only the vaccine, and the rest received the vaccine in addition to treatment with bevacizumab, which suppresses the growth of blood vessels in the tumor (10 people), or treatment with bevacizumab and the chemotherapy drug cyclophosphamide (the remaining 10 people). In addition to the standard assessment of the patient's condition, the development of an antitumor response at the cellular level was checked. Therapy and follow-up were carried out for two years.
During the study, 392 doses of the vaccine were administered to the patients in total. It turned out that it is well tolerated, has no serious side effects, and indeed leads to the development of an immune response against tumor neoantigens. However, it turned out to be impossible to exclude from the chemotherapy treatment regimen – in the group even receiving bevacizumab, only three out of ten women survived for two years, while in the group receiving cyclophosphamide, eight women survived.
Survival rate of patients treated with different courses of therapy.
Cy – cyclophosphamide, Bev – bevacizumab, OCDC – vaccine.
In order to evaluate the effectiveness of adding the vaccine to chemotherapy, the researchers calculated the survival rate among former patients of the center who were treated with a combination of cyclophosphamide and bevacizumab – there were 56 such people. Within two years of treatment, 50 percent of these women died. At the same time, in the experimental group that additionally received the vaccine, the survival rate was 80 percent. Thus, vaccination at first glance turned out to be effective. However, due to the fact that the sample of women who received both chemotherapy and the vaccine consisted of only 10 women, the statistical significance of this result is questionable. The researchers will have to find out the real effectiveness of vaccination in recurrent ovarian cancer in future clinical trials on a larger number of patients.
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