Take the tumor in a pincer
A double blow to cancer
A young Russian company has taken a swing at a new method of treating cancerGalina Kostina, "Expert" No. 14-2012
A young Russian company has taken a swing at a new method of treating cancer. Its specialists decided to combine two unique technologies to arm the immune system against tumor cells and at the same time disarm the protection of the tumor itself.
Scientists have made notable progress in the fight against cancer: in creating precisely targeted means to attack tumor cells, in improving methods of radiation therapy, however, cardinal breakthroughs in oncology have not yet occurred. Tumor cells are cunning and persistent, they have a lot of methods of protection. They can secrete a variety of substances that can, for example, make a tumor insensitive to a specific drug or disarm cells of the immune system. Recently, scientists have been trying to find new ways to influence the immune system. A subsidiary of the HimRar High Technology Center, the young company NewVak, is also working in this direction. It combines two technologies, one of which activates immunity against the tumor, the second – removes the protection of the tumor from immunity.
Immunity and tumorIt is known that in a healthy body, tumor cells appear constantly, they are caught and destroyed by the natural guardian – the immune system.
Why in cancer patients it ceases to recognize these cells and allows the tumor to grow, it is not yet known for sure. With the growth of the tumor, the immune system weakens. Presumably, tumor cells have such an effect on immunity.
Scientists have been studying the influence of the immune system on cancer since the beginning of the XX century. The famous founder of the theory of acquired immunity, Paul Ehrlich, tried to inoculate human tumor cells in mice and somehow influence them. Two wars interrupted many studies. It was only in the late 1950s that scientists returned to the topic of oncoimmunology. Numerous studies have been conducted on the effects of so-called immunocompetent cells on tumors. There are a lot of them in the body, but the successes were very modest. Only interferon-alpha gave good results, and then in narrow niches: with kidney cancer that does not respond to traditional therapy, and melanoma after radical removal to prevent the risk of metastases. In the last decades of the XX century, with the discovery of some mechanisms of the occurrence of various types of cancer, high-precision chemotherapy drugs, so-called targeted drugs, began to appear, showing high efficiency. The interest of companies in immune drugs was almost lost, although scientists and clinicians understood that they needed to look in all directions, because different types of tumors and tumors at different stages of their development should be tried to act by different methods – chemotherapy, surgery, radiation, immunotherapy.
The next stage in the development of oncoimmunology began with the accumulation of new knowledge twenty years ago, reports appeared in the press about the development of vaccines and drugs based on antibodies or cells of the immune system – T-lymphocytes. Vaccines are designed to stimulate your own immune system to fight tumor cells, antibodies and T-lymphocytes – to act as additional units of fighters for immunity. Vaccines are being developed most actively now. According to analysts, more than a hundred vaccines are in development at six dozen companies. There are only two vaccines registered in the world: one in the USA (Provenge) for the treatment of prostate cancer, the other (also American) – in Russia. The latter is a vaccine for the treatment of renal cell carcinoma of the well–known American biotech company Agenus called "Oncophagus".
We started with a transferThe NewVak company, created not only for the development of its own funds in oncoimmunology, but also for the transfer of proven technologies in a selected area, of course, paid attention to both vaccines, but to a greater extent – to the one registered with us.
Of course, the fact that the American vaccine was not registered in the USA was alarming. "NewVak" meticulously studied the reasons. It turned out that the Agenus vaccine was not approved in the United States because the developer company did not fulfill the procedural conditions for the third phase of clinical trials imposed by the American Food and Drug Administration (FDA). The FDA considers the effectiveness of the drug in relation to all patients suffering from the disease, and data on the effectiveness were presented only from the group of moderate renal cell carcinoma. However, NewVak also carefully studied the opinions of clinicians from around the world who took part in the trials. In their opinion, the vaccine can be very effective in the treatment of various groups of patients and promising in the treatment of other types of cancer. At one of the international congresses, Oncophagus was recognized as the best therapeutic vaccine. The Russian company also took into account the fact that out of 750 patients who participated in the trials, 200 were from Russia, and domestic specialists also highly appreciated Oncophagus.
However, after registration in Russia back in 2008, the "Oncophagus" has not yet been used for medicinal purposes. The reason is technical and logistical difficulties, as well as the cost of the drug. The fact is that "Oncophagus" is a personalized vaccine and cancer cells of a particular patient are required for its manufacture. When clinical trials took place, the cells of patients from different countries were sent by plane to the Agenus production site in Lexington, Massachusetts, and then the finished vaccines were returned to the clinics. It is clear that this is a complex and expensive process.
"NewVak" literally decided to bring the vaccine closer to Russian patients by moving the technology and production from Lexington to Khimki. In December 2011, a licensing agreement was signed with Agenus on the transfer of technologies for the development and production of the Oncophagus vaccine in Russia. Agenus found the deal profitable: firstly, NewVac will expand the field of vaccine application in other areas of oncology (in the treatment of melanoma, lung cancer, glioblastoma), as well as in combined treatment methods; secondly, if successful, Oncophagus itself and in combination receives the fast-growing market of Russia and the CIS and it can step from this market to the world, having received the necessary array of efficiency results.
Already, the company is preparing a site for the production of Oncophagus on the basis of HIMRAR, which will have to be certified by both Agenus and the relevant Russian authorities. The release of the vaccine may begin as early as this year. It is clear that innovative drugs produced in Russia will cost several times cheaper than imported ones.
Joint work with Agenus, according to the chairman of the board of directors of the company "NewVak" Nikolay Savchuk, does not end with the signing of the agreement. The companies will work in close cooperation both in the field of further R&D, as well as in the training of specialists and the transfer of production know-how. From day to day, NewVak will begin clinical trials of Oncophagus in new areas and in combination therapy. Combination therapy is the most promising direction of the company's development.
Tricky tumor protectionOne of the incentives for the creation of "Newvak" was the acquaintance with an interesting theory of one of our outstanding compatriots abroad, Professor Mikhail Sitkovsky, who works at the Dana-Farber Cancer Institute at Harvard Medical Center in the USA and heads the Institute of Inflammatory Diseases in Boston.
He suggested, and then showed in experiments on rats, that a tricky tumor is protected from the immune system in a peculiar way. It produces adenosine molecules that bind to the receptors of cells of the immune system – T-lymphocytes. Adenosine causes a cascade of reactions in lymphocytes, after which they seem to forget that they were going to fight this tumor. It was logical to assume that the creation of some synthetic molecules that would interfere with the connection of adenosine with T-lymphocytes would be able to remove the protection of the tumor from the immune system.
Newvak decided that such molecules, the so-called co-adjuvants, would be perfectly combined with vaccines. After all, the effectiveness of vaccines may not be so high if the tumor is constantly protected from attacks by the immune system. "Personalized vaccines are a new word in oncology. They do not generally enhance the immune response, as, for example, interferon-alpha, but teach the immune system to fight a specific tumor,“ says Andrey Golubev, medical director of NEWVAK. – The co-adjuvant, as it were, works behind enemy lines, punching holes in the defense of the tumor. Acting together, the vaccine and the co-adjuvant can dramatically increase the survival rate of patients."
Now in "Nuface" create a series of co-adjuvants, and it is progressing well, however, the development of new molecules is known to last at least ten years. While their products Mature, the company decided to save time by finding in the clinical trials of one of the foreign companies, the drug that can be used as a co-adjuvant in combination with the vaccine. Istradefylline currently being tested in the third phase in the treatment of Parkinson's disease, but its effect is similar to our researchers (in neurology it blocks corresponding receptors of neurons in Oncology – receptors of T lymphocytes). Istradefylline has already proven its safety and effectiveness, so the "Novak" decided to use it in conjunction with "Ancoragem".
"We have studied an interesting development of anticancer vaccines, which are conducted in the Institute of Oncology. N. N. Petrova in Saint-Petersburg and Ronce them. N. N. Blokhin Moscow, – says Nikolay Savchuk. And agreed about cooperation with them when testing these vaccines in combination with istradefylline, and then and our own, more powerful and effective, in our opinion, co-adjuvants".
A promising direction of combined technologies allowed "Novaku" to become a resident of SKOLKOVO. The research part of the project, the company will receive 200 million rubles and will invest 91 million of its own funds, the establishment of production and commercialization will be funded by a "Novacom" due to additional investments of its own. "If successful, Russia will have a unique pioneering technology for cancer immunotherapy, which can be replicated around the world, – says Nikolay Savchuk. We are at the forefront of such studies. Commercial niche in the world just opened, however, according to analysts, in 2014, the market antitumor vaccines may be more than 600 million dollars."
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09.04.2012