How will gene therapy help

Innovations in oncology

Dmitry Mungalov, Sk.ru

The biomedical cluster of the Skolkovo Foundation is preparing for publication the first popular science almanac in Russian dedicated to genome editing. The authors will be leading Russian-speaking scientists working both in Russia and abroad. 

Until now, a reader in Russia who wants to get acquainted with the latest advances in the field of genome editing had to either study specialized foreign journals, or be content with presenting news in our media, and the level of reliability of these retellings could be different.

The issue of the almanac "Genome Editing" (taking into account the specificity of the topic, it is quite clear that it will be more scientific than popular) is timed to the Russian Cancer Congress, which will be held on November 15-17 in Moscow at the CROCUS EXPO International Exhibition Center. "We have assembled an extremely interesting team of authors who deal with various issues of genome editing – both from the point of view of scientific approach, clinical practice, regulatory and ethical aspects. Despite the fact that the almanac will be published before the Russian Cancer Congress, there will be no focus on oncology in it, although Pavel Volchkov from MIPT, a participant in Startup Village-2016, wrote an article about modeling the immune response using gene editing to stimulate antitumor immunity, – said Sk.ru Kristina Khodova from the biomedical cluster of the Skolkovo Foundation, Director of the Competence Center in Oncology. – The almanac will include articles about genome editing for the treatment of HIV infection and hereditary diseases. The authors also describe the main editing technologies associated with different types of nucleases. So, an article about the research of the nuclease of "zinc fingers" (zinc finger, one of the protein structures used in genetic engineering; its clinical studies for the treatment of HIV infection are taking place in the USA) was written by one of the developers of the method Fedor Urnov."

The program of the biomedical cluster at the Russian Cancer Congress (November 16) will also be devoted to the issues of genome editing. "This is a relatively new topic in clinical application," continues Kristina Khodova. – Although the technology has been developed for a long time, its clinical trials have just begun. So far they are isolated, but their potential in the treatment of hereditary diseases, HIV infection, immunotherapy of oncological diseases is already clear."

When organizing its program within the framework of the congress, the Foundation traditionally cooperates with RUSSCO, the Russian Society of Clinical Oncology. Skolkovo has been participating in the Russian Cancer Congress for the 4th year, and we are always grateful to our colleagues for the fact that they value our relationship and always give us the opportunity to tell in detail about the activities of the Foundation and the achievements of our startups," the interlocutor lists Sk.ru – As usual, we will organize a demonstration stand where the developments will be presented our residents in the field of diagnostics and treatment of oncological diseases".

Another traditional element of the Skolkovo program at the congress is the OncoBioMed competition, which this year will be organized for the third time in partnership with RUSSCO and the Russian Academy of Sciences. According to Kristina Hodova, "the winners of the first two years became residents of the Skolkovo Foundation, they all quite successfully found various sources of funding, including grant support from the Foundation, and made significant progress in their developments."

One of these teams, AGICITY (AGCT), which won the therapeutic nomination of the OncoBioMed competition last year, is successfully developing a technology for transplanting altered cells of the patient himself for the treatment of HIV-associated malignant tumors. The mentor of this team was Mikhail Samsonov, chairman of the Onkobiomed jury, Director of the medical department of the R-PHARM Group of companies. Subsequently, AGICITY took second place in the competition at the Startup Village-2016 conference; the company actively cooperates with colleagues from the University of Hamburg.

Kristina Khodova considers the dynamic development of the AGICITY team to be a notable event in the activities of the Competence Center in Oncology headed by her. "A big step forward is due to the fact that other promising companies have joined the list of our residents, in particular, UNIM, which became a member of Skolkovo after last year's oncocongress. Successfully developing a digital platform for pathomorphological diagnostics, UNIM stands guard over the correct diagnosis in cancer patients. Despite all the advances in the field of diagnostics, histological studies are still the only method to confirm the diagnosis. They are complex and often subjective, largely depend on the experience and qualifications of the pathologist and at the same time directly affect the treatment strategy. So, according to the specialists of "UNIM", about a third of the diagnoses that come to them for verification are incorrect. This catastrophic figure confirms the need for a collegial approach to diagnosis."

K. Khodova calls the entry into the first phase of clinical trials of a drug developed by Fusion Pharma for the treatment of resistant forms of chronic myeloid leukemia, as well as the achievements of Rusfarmtech, which introduces a low-molecular-weight fibroblast growth factor receptor type 2 inhibitor to the market, other examples of successful activities of residents of the Competence Center in Oncology. The drug has been offered the international nonproprietary name "Alofanib". The Rusfarmtech team has completed preclinical studies and is entering the first phase of the clinic, studying the effect of the drug on patients with stomach and ovarian cancer. In total, about a dozen and a half drugs developed by residents of the Competence Center in Oncology of the Skolkovo Foundation have reached the stage of clinical trials. In total, about 70 residents of Skolkovo are developing innovative products in the field of oncology. The revenue of the companies included in the Competence Center in Oncology in 2015 exceeded 1.6 billion rubles; over the past year, more than 80 intellectual property objects have been registered.

Returning to the program of the Russian Cancer Congress. Traditionally, within the framework of this forum, promising directions in the treatment of oncological diseases are discussed, one of which in the last couple of years is considered a symbiosis of cell therapy, genetic engineering and immunotherapy – the technology of using autologous T cells with a chimeric receptor (CAR-T). The essence is as follows: immune T cells are taken from the patient's blood, they are trained to attack cancer by reprogramming for the synthesis of the chimeric antigen receptor CAR, which recognizes tumor cells, and CAR-modified T cells are introduced back into the patient's body. According to Forbes magazine, the technology marks "the beginning of a new era in antitumor therapy, when the effective use of high-tech immunotherapy methods gave hope that tumor diseases can be defeated using CAR-T technology." This is one of the most interesting modern approaches in the treatment of oncological diseases, confirms Kristina Khodova. "The first clinical studies of this technology were conducted by the University of Pennsylvania, as well as Juno Therapeutics and Kite Pharma. The frequency of complete responses in the first experiments exceeded 80%. This is a very good indicator: the new method was mainly used by patients who do not respond to current therapy, or who have suffered a relapse of the disease."

Among the residents of Skolkovo there is a startup whose technology is potentially applicable for CAR-T. The company "Siemji Strategy" is engaged in self–delivering RNAs - this is one of the ways to modify CAR cells. Representatives of "SIAMJI Strategy" (its parent company hails from the American Boston) participated in last year's oncocongress, where they met with colleagues from St. Petersburg. Now they are working together on a protocol for a potential study, which may become one of the steps towards the introduction of new immunotherapeutic methods, including CAR-T, in Russia.

No matter how promising this technology may seem, it is unlikely to become a panacea in the treatment of oncological diseases. "Firstly, not all patients respond to it. And the most important thing that worries the clinical community is the presence of serious side effects. Active stimulation of the immune response is fraught with the fact that the immune system begins to react, including to healthy cells, which sometimes leads to the so-called "cytokine storm", manifested by inflammatory processes, fever, low blood pressure. This summer, Juno Therapeutics reported three deaths due to neurotoxicity, and the FDA was briefly forced to suspend these studies. This was another proof of the downside of the use of promising technologies, through which we are introduced into complex and subtle systems of the body," says Kristina Khodova.

She predicts that despite advances in the field of oncology, surgical operations, radiation and chemotherapy will remain the main methods of countering tumors in clinical practice for several more decades. "These methods are progressing: for example, new targeted drugs for chemotherapy are emerging, and one of the first breakthroughs in oncology is associated with them. Targeted drugs have significantly increased the survival rate of patients with many diseases: breast cancer, kidney, lung, chronic myeloid leukemia."

Portal "Eternal youth" http://vechnayamolodost.ru   15.11.2016