- Peter Mikhailovich, could you tell us what is the essence of your method?
- There are viruses that can suppress cancer. They have oncolytic properties. And they are harmless to human health. This method of treatment gives almost no side effects. Only a short-term increase in temperature is possible, which is a positive sign, indicating that the virus has taken root in the body and is having a reaction. It is easily removed by conventional antipyretic agents.
- When will the method become widely used in practical medicine?
- Now our main task is to certify those drugs that we have. This work is supported by the Ministry of Health and the Ministry of Education. We have several grants under which we test these drugs. We are making new variants of oncolytic viruses with enhanced properties. Preclinical trials should begin soon at the Smorodintsev Institute in St. Petersburg. We have already transferred drugs there. Doctors say it will take five or six months to test. Given the situation with coronavirus, I think that tests can be completed at the beginning of the 21st year, and then we can already negotiate with the clinics about conducting clinical trials.
- What is the drug that should be tested?
- A drug is a live virus that is grown on cell cultures. This is a new type of medicine that does not need much. It is important that it enters the body in those cells that are sensitive to it. And then he reproduces himself. That is, the medicine reproduces itself in the place where it is needed. This is a solution, 100 million viral particles in one milliliter. But the biggest problem with this treatment is the way the virus is delivered to the tumor, in the case of glioblastoma, to the brain, to the area where the tumor is located.
If the drug is administered simply intravenously, then a very small part of the virus can enter the tumor. In the bloodstream there are nonspecific factors that quickly inactivate this virus. In addition, the brain has a blood-brain barrier that prevents any unwanted agents, including viruses, from entering it. Therefore, the virus is very difficult to get to the tumor.
- Peter Chumakov
- How did you solve this problem?
- We have developed another delivery method - using the immune cells of the patient himself. For this, the patient’s blood is taken, the components of the so-called “white blood” - leukocytes - are released from there. They contain a lot of different types of cells. In order to isolate the cells necessary for us, which can go into the tumor in a directed manner, we carry out the fractionation of this “white blood”. And we force a certain fraction, monocytes, to differentiate into dendritic cells. Then we infect these dendritic cells in vitro with the oncolytic virus, and inject them intravenously.
These cells, like torpedoes, go to the foci of inflammation where the tumor is located. There, the virus emerges from them and begins to kill the tumor cells. We have already worked out this method on several patients. There are good examples when an MRI or CT scan shows how the tumor shrinks and disappears. But this is not happening at all.
“Why can't the same viruses cope with the same types of tumors?”
- The fact is that each specific virus in our panel affects only 15-20% of patients. The rest are resistant to the virus. However, we have many different viruses, and we can choose one for any patient. But for this you need to have living cells of the patient.
Now we are developing such tests that can quickly show by ordinary biopsy which virus the tumor will be sensitive to. This is a very difficult job. Perhaps in the future, special clinical laboratories will receive from patients all the necessary materials, and in the conveyor mode conduct testing, select drugs, and then - treatment.
But now we are being approached by those whom no one can help anymore. Some of them are treated with us for six months or more. If there is stabilization, and it is clear that the tumor does not grow, we take a break until the growth resumes. But there are cases when growth does not resume. We have a patient who has been living for four years, despite the fact that he had no chance. Glioblastoma is a fatal disease, the average life expectancy with it is 12-15 months from the moment of diagnosis.
- Peter Mikhailovich, on May 14, at a meeting on the development of genetic technologies in the Russian Federation, director of the Institute of Molecular Biology named after V.A. Engelhardt Alexander Makarov told the president about your treatment methodology, and cited Anastasia Zavorotnyuk, who made a selection of viruses that could defeat her disease, as an example. After that, the heroine of one of our previous materials, Ekaterina Kalashnikova, turned to us . In a letter she wrote that she represents “a group of patients in the amount of 400 people and their relatives”. She wondered how to get to you for treatment. Do these people have the opportunity to receive such treatment?
-First of all, I must say that so far this is an experimental treatment. When Makarov reported on this method at a meeting with the president, it seems to me that he did not expect that this would cause such a resonance. Now I am literally attacked by letters from dozens of patients asking for help.
It seems to me that it was not worth talking about Zavorotnyuk. I know that the relatives of Anastasia for a long time did not comment on her condition at all, and did not want the press to raise this issue. I myself have never seen Anastasia. Her relatives approached me asking for help. I said that we could at the first stage test its cells.
The fact is that during the operation, live tumor cells were taken and transferred to one of the institutes, where they were able to bring them to the cell culture so that they could be shared in vitro. We took them and tested for sensitivity to our oncolytic viruses, which we consider to be a treatment for glioblastoma. It was found that out of 30 viruses, 7-8 are quite suitable. And at this stage we stopped, because the husband of Anastasia Pyotr Chernyshov said that now the situation is more or less calm, if there is an urgent need, they will turn to us. That's all for Zavorotnyuk.
But all this we have done and are doing on a very limited scale. Now, when everything has come out in the media, we simply can not cope with such a shaft of patients.
- Can you comment on the dependence of IVF and the appearance of glioblastoma? Is there such research?
- As I understand it, this issue was again raised by the history of Zavorotnyuk. In this case, she had IVF. But this does not mean that there is any connection. Firstly, IVFs do not do much, and glioblastomas account for 1% of all tumors. Glioblastoma is found not only in women. I think there is no connection. After all, how can IVF affect? The level of sex hormones rises. But those hormones, which are quite physiological and always are in the body. They just appear at a different time and in a different dose. And they are unlikely to have an effect on glial cells so that they are reborn.
- In the world are similar studies on the treatment of glioblastoma? What do you know about this?
“We are not the first to test viruses for glioblastoma.” Now this is a very hot topic all over the world. And different viruses are being tested to treat different oncology in many countries. I know one case that was started to be treated in the 96th year with the Newcastle disease virus, this is a bird virus. And the patient still lives with glioblastoma. This is published data. And there are several more cases of treatment with recombinant herpes viruses.
Last year, a very sensational work came out that 20% of patients with glioblastoma can be cured by a recombinant polio virus vaccine.
But neurosurgeons are conservative people. They would never agree, even as an experiment, to conduct such experiments in humans. Because they are very at risk if there is a complication. Therefore, we must wait for preclinical trials in order to then convince them to try the scheme with direct introduction of the virus directly into the tumor.
- © KATERYNA KON / SCIENCE PHOTO LIBRARY
- And who and when did they first notice the effect of the virus on cancer cells?
- Back in the early 20th century, scientists noticed that tumor cells reproduce viruses especially well. After infectious viral diseases, some patients with various types of cancer experienced remissions. And even then the idea arose that in the future it would be possible to treat cancer patients with viruses.
In the 1950s, experiments were conducted in America to treat cancer in hopeless patients using pathogenic viruses. It was believed that this is a lesser evil compared to cancer itself. And then positive results were obtained. But since many patients were dying from infectious diseases, a very large resonance arose. Doctors who started doing this have discredited this entire area for years to come. Additional ethical rules were introduced. The mere mention of the fact that the virus can treat cancer, has become a taboo.
In the 90s, it became clear how viruses are structured, their genome structure. Scientists have learned to introduce changes in the genome of viruses to make them harmless. And then, the worldwide boom in the development of virus-based drugs for cancer treatment began. But here is a new misfortune. Pharmaceutical companies began to resist this. Because this is a completely different treatment that undermines the basis of their well-being.
At the beginning of the 10s of our century, many small companies developed drugs, which then underwent some kind of clinical trials, some promising properties were shown. But pharmaceutical companies bought up these developments, and practically stopped the activities of these small startups.
- Did anyone manage to overcome the pharmaceutical lobby and register the drug?
- Now in the world three drugs of oncolytic viruses are registered. One drug is approved for use in the United States for the treatment of malignant melanomas. Another recombinant adenovirus in China, and one enterovirus in Latvia. But, in general, each of these drugs is still very limited in use, due to the fact that they all affect only a part of patients.
- Peter Mikhailovich, how long have you been conducting your research?
- All my life, since the 70s. I had a time when at the beginning we knew almost nothing about viruses. And as we learned something, we made some contribution to this science, and we studied. And I started with viruses. Then he switched to the problem of cancer - the fundamental mechanisms of cell division: how a normal cell turns into cancer. And then he returned to virology.
I must say that my parents were virologists, they were engaged in the polio campaign. In the 70s, my mother studied how antibodies to polio vaccine are formed in children, and she found that many children do not form antibodies. It turned out that in the intestines in children at this time there was an asymptomatic infection of another harmless enterovirus. And it caused nonspecific protection against the polio virus. Therefore, vaccine poliovirus could not induce antibodies in these children. These harmless viruses have been isolated from the intestines of healthy children. And on their basis, live enterovirus vaccines were created, which were tested in order to prevent some other unknown infections.
And so we decided to resume the approach that my mother proposed when using the enterovirus panel. It turned out that those patients who are not sensitive to one virus may be sensitive to another. There was an idea of selecting a virus for a patient. We have developed a whole panel of our own viruses, which may also have enhanced properties. We are continuing this development.
- Your viruses can defeat cancer. Are there viruses that cause tumor development?
- Yes. For example, cervical cancer in 95% of cases is caused by the papilloma virus. Now there are even vaccines against oncogenic papillomoviruses of the 16-18th serotype, which are used for girls so as not to get cervical cancer. But this is the biggest example. In most cancers, the viral nature can now be completely ruled out.
- Do you use natural viruses or construct them?
- We have different viruses. As I said, the first panel was isolated from the intestines of healthy children. These are natural non-pathogenic viruses, which, incidentally, protect children well from many viral infections. In addition, we make synthetic and recombinant viruses when we introduce certain changes in their composition that enhance their oncolytic properties.
- There are still places on the planet where there can be a lot of viruses, which we still have no idea about. For example, those that live in the deep ocean. What do you think, if suddenly someone undertakes to study the ocean, precisely from the point of view of viruses, there might be useful for you there?
- Yes, and now this is also a very hot topic. When they developed a method for sequencing genomes, DNA, RNA, the temptation arose: to filter waste water, ocean water, from ponds, seas. We have already drilled a well in Antarctica to the ancient lake to see what is there and to isolate biological components from there and to sequence them. And it turns out that we are surrounded by a huge number of viruses that are absolutely harmless. And the impression is that our initial idea of viruses as something harmful and causing only disease is wrong. A pathogenic virus is the exception rather than the rule.