Anti-cancer vaccine: a war on two fronts
Double-action vaccination against cancer
A vaccine has been created that simultaneously kills cancer cells and stimulates the immune systemNadezhda Markina, <url>
Cancer immunotherapy is a relatively new direction.
A cancer tumor, as well as bacteria or viruses, can be fought with a vaccine that incites the immune system against its own cells, which have "gone crazy", genetically changed and began to divide unrestrainedly. These vaccines are not preventive, as against influenza or tuberculosis, but therapeutic – they are administered to an already ill person to help the immune system cope with the disease. An antitumor vaccine can contain whole cancer cells – these are cellular vaccines. And it can carry an antigen protein or DNA/RNA encoding it as part of a viral vector. The role of such a vaccine (like any vaccine) is to train the immune system to recognize the enemy.
Viruses gave rise to another approach to cancer treatment called viral oncolysis. The idea is to use the ability of the virus to kill (lyse) the cells in which it multiplies.
The idea itself arose a long time ago: the first attempts to implement it date back to the 50s of the last century - the treatment of cervical cancer with the help of adenoviruses. In Russia in the 60-70s, they tried to use non-pathogenic strains of enteroviruses for the treatment of oncological diseases. But due to the ambiguity of the mechanism and technological difficulties, the attempts were stopped. They returned to research on this topic in the 90s, since then experts have been looking for candidate viruses and describing their interaction with cancer cells.
In a new article published in the journal Science Translational Medicine (Kim et al., Oncolytic and Immunotherapeutic Vaccinia Induces Antibody-Mediated Complement-Dependent Cancer Cell Lysis in Humans), scientists write about the trials of the Pexa-Vec vaccine.
This is a fourth-generation vaccine, both oncolytic and immunotherapeutic. It is made on the basis of a weakened and genetically modified cowpox virus.
The gene of the enzyme thymidine kinase is damaged in the vaccine virus, so the virus can multiply only in a cell with high thymidine kinase activity, namely, this is the biochemical label of cancer cells. As a result of the reproduction of the virus, the cell membrane is destroyed – the cell "explodes", lysis occurs. At the same time, the modified virus carries the gene of the GM-CSF protein (human granulocyte-macrophage colony-stimulating factor), which stimulates the immune response, enhancing the reproduction of lymphocytes.
Phase 1 of clinical studies showed that the vaccine virus multiplies in the tumor, synthesizes the GM-CSF protein and stimulates lymphocytes. Now the scientists wanted to investigate whether the vaccine causes cancer-specific antibody formation.
First, they studied this on a model of rabbits with vaccinated tumors: after vaccinating rabbits, blood plasma was collected from them at different intervals and cancer cells were placed in it. These cells in the plasma died starting from the 18th day after vaccination. Since the immunized plasma increased the content of antibodies – immunoglobulin G, the researchers concluded that the rabbits developed a cancer-specific immune response. The antibodies attached to proteins on the membrane of cancer cells and triggered their destruction.
Plasma from vaccinated rabbits was injected into other rabbits with vaccinated liver tumors. As a result, those began tumor necrosis. Rabbits treated in this way gained weight and lived longer, while untreated rabbits got sick and died.
At the next stage, the effect of the vaccine on three patients who received it during clinical trials was investigated. After vaccination, one patient with renal cell carcinoma lived 76 months, another patient with small cell lung cancer - 24.5 months, the third with melanoma - 12 months. This is longer than they could have lived without vaccination, taking into account their condition, according to doctors.
Blood plasma was taken from vaccinated patients and cells of different types of cancer tumors were placed in it. As in the case of rabbits, cancer cells in the immunized plasma began to die, and the most vulnerable were cells of the same type of tumor from which the patient suffered.
The results of the study confirmed that the vaccine really works on two fronts and causes cancer cell lysis and antibody formation at the same time. This will help scientists in developing future cancer vaccines.
Portal "Eternal youth" http://vechnayamolodost.ru20.05.2013