Funding for trials of the Russian melanoma vaccine has been stopped
Cancer vaccination
With the help of his drug containing two types of microorganisms, Kohli tried to cause the body's immune response to the tumor. For a hundred years, the methods of creating antitumor vaccines have changed a lot.
Sergey Kiselyov, Professor, Doctor of Sciences, Head of the Laboratory of Genetic Foundations of Cellular Technologies at the Institute of General Genetics of the Russian Academy of Sciences, told Medical News about the process of developing a therapeutic vaccine against melanoma (skin cancer) and the results of its testing.
The ideology of the vaccine, which we started testing in 2000, is as follows: to show the immune system that a tumor cell has features, let's say, pathogens that should activate innate immunity.
The fact is that it is very difficult to make the immune system react to a malignant neoplasm.
Since the tumor arises from the tissues of the human body, it is not recognized by innate immunity, the launch of which is necessary to activate adaptive immunity.
To activate innate immunity, we used a gene discovered in our laboratory called PGRP, encoding the Tag7 protein – it is a mediator of innate immunity.
Tumor cells of mice were taken, genetically modified with the help of the PGRP gene – the resulting cells and served as a vaccine. To prevent the modified cells from growing, we irradiated them. The cells inactivated in this way could not divide, but they could exist for some time (the so-called dead vaccine).
It turned out that a malignant neoplasm presents tumor antigens to the body's immune system, to which a response occurs, and the protein whose gene we introduced activates the innate component of the immune system. So we got a genetically engineered antitumor vaccine against melanoma. All this happened within the framework of a program funded by the former mayor of Moscow, Yuri Luzhkov.
What are the functions of this protein? In the course of experiments (including on monkeys), it was proved that this protein activates monocytes and dendritic cells, and is also to a certain extent a chemoattractant.
We needed two of its functions listed above – activation of monocytes and dendritic cells, since they represent an immunological component to other cells of the immune system. The latter, learning from this, trigger or do not trigger an immune response for one reason or another (if a dendritic cell has "eaten" something "of its own", it should not be activated, otherwise an autoimmune response will occur). The protein of the gene that we injected into cancer cells led to the activation of immune cells. The cells were trained and then reacted to similar tumor antigens that were present in the malignant neoplasm. That was our ideology.
Have clinical trials of a genetically engineered vaccine been conducted? If so, what are their results? Clinical trials of the first and then the second phase were started.
They were held at the Moscow Blokhin Research Center and at the Petrov Research Institute of Oncology in St. Petersburg. We got good results: patients showed inhibition of tumor growth, and in some cases even regression of the disease.
We then embarked on a difficult and difficult path of personalized medicine, because for each patient we made his own, personal vaccine. We took tumor material from each of them, grew these cells in culture, then made genetic modification, analyzed, and after some time received a vaccine. This process is quite complicated, because not every patient, even if there is tumor material, can grow his tumor cells in culture – this is possible only in 25-30 percent of cases.
Personalized medicine is great, but still, it's probably a matter of the future. Therefore, we have slightly changed our ideology and decided to make a universal vaccine, even if it is less effective. To do this, it was necessary to select such tumor antigens that would be present in a large number of tumors. We started to follow this path, but, unfortunately, it has not been developed now for a number of reasons, including financial ones.
The ideology is this: we make one tumor cell line as a producer of our protein (a standard preparation), and then mix it with the patient's tumor material. Not with cells, but simply with tumor material immediately after its removal. It turns out that the modified cells carrying "their" antigens act as donors of the Tag7 protein, and the patient's tumor tissue acts as an antigen donor. What we had to do was to go through, again – these are the rules of the game in medicine – clinical trials. First, we launched clinical trials of the standard component of the antitumor vaccine – genetically modified tumor cells. We called this component "Melovac" (a combination of melanoma – vaccine).
In fact, due to the existing standards, the tests are quite difficult. To participate in the first and second phase of clinical trials, it is necessary to recruit volunteers with the most advanced forms of the disease, for which other types of therapy have been exhausted. And this is despite the fact that the ideology of tumor vaccination concerns postoperative patients, the appearance of secondary tumors and metastasis. But according to the rules, we should take into research people who have a good progressive tumor process, who are already inoperable, and "chemistry" does not particularly affect them. This significantly increases the cost and lengthens the process.
The first clinical trial took us about three to three and a half years, the first phase of the second stage of clinical trials lasted two years, now we have been working on the second phase for almost three years, which ended in 2012. But the program in which all this was carried out also ended. Due to the completion of the program, the Moscow government has so far refused to pay any money for the past year, although we have completed the second stage of clinical trials and a number of other works. Most likely, these works will not be paid for in the future, so it is unlikely that our entire vaccine will receive any use. If these trials had been completed, we would have continued developing the vaccine.
And yet, how many people participated in clinical trials and what is the effectiveness of the standard vaccine?As far as I remember, about 40 people passed in the second phase.
More than 70 percent of patients have an immunological response to the vaccine, that is, it stimulates an immune response against tumor cells. In about 30 percent of patients, we observed a slowdown in the progression of the disease, and in isolated cases, a partial regression of the tumor, that is, the direct effect of the vaccine.
Here, very serious patients participated in the trials, as well as only the basis of the vaccine, to which we did not expect a strong response. But we have seen that it stimulates the immune system.
In general, our vaccine works. However, against the tumor that the patient has, it does not work very well, because patients are in a fairly advanced stage of the disease. And the only thing that immunization leads to is to slow down the progression of the disease, which is also an important parameter. During a break in chemotherapy, we would like to support the body so that there is no further development of the disease. During this period, other means of exposure can be used – for example, a vaccine that can help with this. This gives additional time for doctors to find and apply some other means.
Portal "Eternal youth" http://vechnayamolodost.ru01.02.2013