The first Russian gene-therapeutic cancer drug is being prepared for clinical trials
Cancer by calculationNikita Maksimov, "Russian Newsweek"
Don't look at what he's like, where he's from, just take him and kill him. In the scientist's office, a photo of him with a toy machine gun on his chest hangs on the wall. "They gave it to me on February 23," says the 70–year-old academician, "and I really like it."
Three years ago, Sverdlov led a project to create Russia's first anti-cancer drug based on gene therapy methods. Scientists, pharmacologists, lawyers and technologists from various scientific institutes and firms joined together in one team. The Ministry of Education and Science has allocated unprecedented funding for Russia – 289 million rubles.
Toxicological tests of the drug on mice are currently underway. This year, scientists hope to complete them and begin the first phase of clinical trials – on volunteers with the last stages of cancer who have nothing to lose. In addition to the drug, a genetic test system will be released, which will allow doctors to make an individual treatment plan for each patient. To enter the market, it will take several more millions of dollars and years of hard work. But scientists are confident that their approach to the destruction of malignant tumors, primarily lung cancer, will lead to the creation of an effective drug.
"This project is unique for Russia," says Aria Biragin, a professor at the Laboratory of Immunology at the US National Institutes of Health, who is developing a cancer vaccine. – Such experience is very useful both for scientists and pharmacologists. If it is possible to really create an effective drug, then Russia will be able to take its rightful place in the drug market."
Almost every week in the leading scientific journals of the world there is another publication describing a new method of fighting cancer. "Hundreds of billions of dollars have already been spent, mountains of articles have been written," says Andrey Gudkov, professor at the Roswell Park Cancer Institute. "We already know quite a lot about cancer, but we don't have to talk about defeating it yet." The problem is partly that it is not possible to draw a target for the medicine in any way. How does the drug determine which cells it should kill?
"Cancer is very multifaceted," says Aria Biragin. – Tumors arise due to the interaction of many genes, and each is unique to the patient. For many years, scientists have been discovering that this type of cancer, at this stage, such and such a protein is released." Unfortunately, the hunt for a marker that would show that the cell has become cancerous and must be destroyed, did not lead to success.
Sverdlov says that he decided long ago to abandon applied research, considering it a waste of time. "But a few years ago I realized that I get satisfaction from the thought that interferon, which we developed second in the world in the 70s, helped millions of people. And I decided at the end to make another drug, from which you can get satisfaction," he says. At the first stage of the work, the team of Evgeny Sverdlov also did not escape the temptation to look for a universal sign that would distinguish a normal cell from a cancerous one. The protein survivin, which is synthesized in most cancer cells and is a very important element for their development, was chosen as a target. But this method did not justify itself.
Over time, scientists have found a way out of the impasse. They decided to fight the tumor with the help of a killer gene. Scientists used a gene that is embedded in a cancer cell and turns the usual antiviral drug ganciclovir into a poison that is fatal to this cell. Ganciclovir can also be injected into the body in tablets or as an injection. The main thing is that the gene is like a virus: it is able to infect neighboring tumor cells without touching the usual ones. "The process will stop only at the border between the tumor and healthy tissue," says Sverdlov. (The diagram can be viewed in enlarged form in a separate window.)
This method has been developed since the early 90s. According to Aria Biragin, there are no great successes so far: it is still easier to cut out cancerous tumors with a scalpel, and not with the help of molecular surgery. "Yes, this approach is used by many scientists around the world," agrees Sverdlov, "the general principle is known. But we have managed to move far enough to create a cure. It seems to us that our approach is correct."
In one of the latest experiments, scientists injected their drug into four mice with melanoma, a skin tumor. "It did not affect one," Sverdlov's graph shows, "the other tumor completely disappeared without relapses, and the other two lived four times longer [compared to the average life expectancy of sick mice]." There was no absolute cure, but if the results obtained are compared with the success of the treatment of cancer patients, then optimism will increase.
The Russian Cancer Research Center of the Russian Academy of Medical Sciences helps geneticists to check theoretical constructions. "We are, in a way, the ultimate instance of what they will do," says Irina Zborovskaya from the RSC. "We have a very large bank of clinical samples from different patients with different types of cancer, at different stages, which is used to test the properties of this drug." Doctors from the Russian Medical Center are also interested in this project because the second part of it is the creation of test systems - chips for the diagnosis of tumor properties.
The test system is a glass plate on which a special gel is applied. The gel may contain up to several thousand molecular probes capable of analyzing, for example, genetic mutations. If a drop of a patient's blood is placed on such a plate, the probes will show whether he has genetic failures or not. "Our laboratory has been developing such molecular biological markers for a long time, which will help doctors to make a prognosis for the treatment of a patient," says Zborovskaya. – They help to determine how long the patient will live, what type of treatment is shown to him. We hope that with the help of such an analysis, doctors will be able to make a "molecular portrait" of the patient and the tumor." With the help of this chip, geneticists are going to adjust their drug to a specific patient.
Now the main task for scientists is to make the drug as safe as possible. "At the first experiments, the mice were so disheveled, swollen," Zborovskaya recalls. – Their kidney function was impaired, they felt very bad." According to Sverdlov, geneticists have already taken into account this negative experience and learned how to get rid of harmful and dangerous impurities. They are now completing the latest toxicological examinations, aiming to start the first phase of clinical trials on volunteers as soon as possible.
"The main thing for us is that the future drug is not toxic," says Yuri Sukhanov, Deputy General Director for Strategy at Binnopharm. "We are looking forward to the completion of the last stage of research." Binnopharm is also a participant in this project. "I thought that I should not have all the money, I should share it with other professionals. Therefore, we have attracted not only scientific organizations, but also those that will be engaged in patenting scientific ideas and their implementation," explains Sverdlov.
The amount allocated for this project is unheard of for Russian medicine, but compared to how much is spent on fighting cancer in other countries, it is not so much, says Aria Biragin. "The creation of an oncological drug costs about $1 billion," says Andrey Gudkov. Sverdlov's estimate is more modest – $250-500 million. Most of the money goes to clinical trials.
"This drug has very good prospects, but only if it is possible to start the first trials. We are very interested in its subsequent production and are ready to invest the necessary funds in conducting all preclinical studies," says Sukhanov from Binnopharm. The fact that patents for this medicine will belong to scientists does not bother pharmacists – the drug will not immediately enter the retail market, it can only be used in hospitals. "It is important for us that there is an order for it from cancer centers and that it be included in state programs. If it is, then it makes commercial sense to bring this development to industrial production," explains Sukhanov. Scientists say that the first target will be lung cancer, and then – if everything works out – other types of cancer.