Virus against cancer
Researchers from the State Cancer Institute in Sao Paulo (Brazil) have successfully used a combination of gene and chemotherapy to fight prostate cancer in mice. For the experiment, the p53 gene was selected as a tumor growth suppressor, which is involved in important cell death processes and is present in DNA in both humans and rodents. Under laboratory conditions, p53 was inserted into the genetic code of the adenovirus. The virus modified in this way was injected into mice directly into tumors that appeared as a result of implantation of human prostate cancer cells. After that, the mice were monitored, assessing the dynamics of tumor growth.
Several groups of mice were used in the experiment. First, an unrelated virus was injected into the tumor as a control. The second group of mice received a modified p53 virus. The third group underwent chemotherapy with cabazitaxel. The fourth group (25% of mice) received a combined treatment: cabazitaxel plus a modified virus.
When the modified virus enters the tumor, it penetrates into the cell nucleus, where it is embedded in DNA and causes its death. The p53 gene was particularly effective in inducing prostate cancer cell death.
Monotherapy with the p53 virus or cabazitaxel had a moderate effect in the form of a decrease in the rate of tumor growth, combined treatment showed the best result – growth was completely suppressed. Subsequent analysis showed that the modified virus not only led to the death of host cells, but also made them more sensitive to chemotherapy.
Tumors are universally treated with chemotherapeutic drugs, but high doses are associated with pronounced side effects. One of them is leukopenia – a decrease in the number of white blood cells in the blood, leading to a weakening of the immune response. In this study, mice were injected with a subtherapeutic dose of cabazitaxel, which was insufficient to destroy the tumor. This was done in order to avoid leukopenia.
The immune system
The destruction of tumor cells using the p53 gene does not guarantee that all cancer cells will disappear, especially metastases in other organs. The researchers set out to refine the technique in order to achieve stimulation of the body's immune system against cancer cells. Since the combination of p53 and cabazitaxel is not enough to activate the immune system, they started looking for another gene that would complement the local effect of p53.
The choice fell on the beta interferon gene because of its exceptional role in the immune response. Interferons are proteins produced by leukocytes and fibroblasts that prevent the proliferation of fungi, viruses, bacteria and tumor cells, as well as activate the defense mechanisms of other cells. The authors decided to combine the p53 and beta-interferon genes to trigger the so-called immunogenic cell death.
Viruses with ARF (a functional analogue of p53) and beta-interferon genes, once in the nucleus of a tumor cell, caused activation of the immune system of mice and recognition of cancer cells as foreign agents that need to be destroyed. When this mechanism is triggered, the immune system fights tumor cells both at the injection site and in tumors located in other organs and tissues.
It should be noted that the genetically modified virus cannot be injected into the bloodstream, only directly into tumor cells.
The main goal of the authors today is to improve the developed approaches, continue experiments and find out whether they deserve to move to the stage of clinical trials in humans.
Article by R. E. Tamura et al. Combination of cabazitaxel and p53 gene therapy abolishes prostate carcinoma tumor growth published in the journal Gene Therapy.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Eurekalert: Genetically modified virus combats prostate cancer.