Anti-cancer viruses
Measles virus will help in the fight against cancer
Cases of sudden cure of cancer patients who accidentally picked up a particular viral infection were recorded later. This phenomenon led scientists to the idea of trying to use viruses – first of all, the measles virus – for targeted therapy of malignant tumors. This area of oncology, called "virotherapy", has long been considered promising in principle, but very far even from human trials, not to mention real clinical practice. Moreover, the same measles virus is by no means safe: from year to year it takes about 150 thousand lives. However, the latest advances in genetic engineering have now made it possible to modify the virus so that it attacks exclusively cancer cells without damaging healthy tissues, and this opens the way to the first trials on patients.
Measles destroys cancer cellsIn recent years, several groups of German researchers have been able to develop their own varieties of these so-called oncolytic viruses.
The head of one of the groups, Guy Ungerechts from the National Cancer Center in Heidelberg, says: "First of all, we modified the virus at the level of the molecular mechanism of its penetration into the target cell. We placed antibodies on the shell of the viral particle, which provide adhesion to strictly defined protein structures on the cell surface. This allows us to achieve a very high selectivity of the action of the virus, to force it to infect only cells whose membranes have the corresponding specific antigens. As a result, our virus infects tumor cells, but healthy ones do not."
The greatest interest of scientists is caused by antigens present on the membranes of so–called tumor stem cells - that special kind of cancer cells, which, according to a number of prominent oncologists, is responsible for tumor metastasis and at the same time almost does not respond to either chemotherapy or radiation. Now a group of researchers from the Paul Ehrlich Institute in Langen, led by Professor Christian Buchholz, has modified their measles virus so that it attacks cells with the CD133 membrane antigen – this glycoprotein is present on the shell of tumor stem cells. Otherwise, the virus behaves like any virus: after infecting a cancer cell, it begins to multiply, the host cell soon dies, and new viral particles infect neighboring tumor cells. "We are dealing here with a unique mechanism of enhancing the therapeutic effect, a kind of domino effect," explains Professor Buchholz.
Another group working with the oncolytic measles virus is specialists from the University Clinic of Tübingen, led by Professor Ulrich Lauer. "In order to increase the effectiveness of the virus in the fight against tumor cells, we additionally armed it," says the researcher. Professor Lauer and his colleagues introduced a special gene into the genome of the virus, which, once inside an infected cell, triggers the mechanism of apoptosis in it, that is, forces it to commit suicide. Thus, the Tubingen scientists further enhanced the oncolytic effect of the virus.
First clinical trialsAll three groups of scientists tested their modified measles viruses on mice.
At the same time, the effectiveness of the virus in the fight against such forms of malignant neoplasms as brain glioma, liver cancer and colon cancer was investigated. In most cases, virotherapy made it possible to significantly slow down the growth of the tumor, and sometimes even completely stop it. Now researchers are preparing to conduct the first clinical trials of a modified measles virus in humans in Europe. Professor Lauer intends to test its effectiveness on patients suffering from liver cancer, especially since similar tests of the oncolytic smallpox virus have been conducted in Tübingen since April 2012.
And Guy Ungerechts in Heidelberg plans to test his measles virus on a very small group of volunteers – less than 20 people – to make sure it is safe. The researcher, however, has no doubt about it, and he has reason to do so: "Our study will not be the first use of the measles virus in human cancer therapy. In the USA, four similar studies have already been performed at the famous Mayo Clinic in Rochester, Minnesota. All of them have been completed, at least 50 patients took part in them, and there were no security problems there."
The vaccine strain of the virus will protect patientsAnd yet the issue of security is by no means an idle one.
Especially if we keep in mind that, say, the CD133 membrane receptor is characteristic not only for cancer, but also, for example, hematopoietic stem cells. In order to minimize the risk of undesirable consequences, scientists use in their experiments not the measles virus that circulates in nature, but a vaccine, weakened strain that children are vaccinated with everywhere. A vaccine virus, as a rule, cannot harm healthy cells, since they are quite successfully defended by interferons. Cancer cells are not able to produce these protective proteins, and therefore they are easily infected even with the vaccine form of the virus. "The data we have today suggests that our modified viruses are no more dangerous than the measles vaccination that has been used for decades," says Professor Buchholz.
However, the application of the new therapy in clinical practice is still far away. According to Guy Ungerechts, it will take about five to six years before the measles virus helps patients cope with cancer.
Portal "Eternal youth" http://vechnayamolodost.ru13.03.2014