25 August 2016

Immuno-oncology in ruble equivalent

Breakthrough drugs for cancer treatment will appear in Russia

Anna Govorova, Infox

It is quite possible that effective innovative immuno-oncological drugs for the treatment of severe forms of cancer will soon be used in clinical practice in Russia, reports Infox. Such drugs have been used in European countries and in the USA since 2011.

The first such drug was finally registered in Russia in the spring of this year, but other medicines of this class will soon enter the Russian market.

However, immunotherapy is a very expensive method of treatment, therefore, to ensure its accessibility for patients, it is necessary to include such innovative drugs in state treatment standards and preferential lists. It is clear that for Russian healthcare, whose budget has already been cut as much as possible, this is a big problem.

In order to somehow get the situation off the ground, the Russian Society of Clinical Oncology (RUSSCO) and the Russian Society of Pathologists (RSP) initiated a program aimed at standardizing diagnostics for new immuno-oncological drugs and identifying patients for whom this therapy will be most effective.

Immuno–oncology is a breakthrough in the treatment of the most severe oncological diseases

One of the key achievements in recent decades, scientists have called targeted therapy, which allows you to "hit" tumor targets without affecting, unlike chemotherapy, healthy cells.

Today, a new breakthrough is called the appearance of targeted immuno-oncological drugs that affect not only the tumor itself, but also "trigger" the patient's own immune system so that it can independently destroy cancer cells.

Immuno-oncology, thanks in part to the achievements of molecular biology, has now reached unprecedented heights. Many experts consider this direction to be one of the most promising in the fight against many oncological diseases, including the most severe ones, for which the prognosis was unfavorable before.

"The emergence of a new direction – immuno–oncology - is, of course, a huge achievement, because finally we began to use the body's own capabilities in the fight against cancer, without bringing something external, namely forcing our immune system to work more efficiently," says Professor, MD, Deputy Head of Scientific the work of the Blokhin Russian Research Center Sergey Tyulyandin.

The tumor is not a passive observer, it knows how to "deceive" the body's immune system

Cancer cells are foreign to the body, so the immune system must recognize and destroy them. For this, nature provides a special mechanism.

Tumor antigens (what distinguishes cancer cells from normal ones) should be presented to the immune cells of the body – T-lymphocytes. To do this, there is a system of representation of the tumor antigen in the body. It is carried out by the dendritic cell. After the presentation has occurred, T-lymphocytes begin to activate and divide. Already having information about the antitumor antigen, meeting with cancer cells, T-lymphocytes destroy them.

This is how it should happen, and this is how it happens in most cases. But at a certain stage, there may be single tumor cells that T-lymphocytes could not recognize and destroy. These cells can form a tumor that is out of immune control.

The fact is that, unfortunately, the tumor is not a passive observer, it knows how to "deceive" the body's immune system, preventing it from carrying out a full–fledged immune response.

To do this, it can secrete special biological substances that suppress immunity. In this case, on the surface of the activated T-lymphocyte, after the cancer cell has already been presented to it, the tumor can express a special antigen – CTLA4. This antigen binds to the substrate on the dendritic cell, and the T-lymphocyte can no longer find and destroy the tumor – the immune response is inhibited.

There is another mechanism when PD1 and PD2 receptors are already expressed on the surface of the tumor itself, which then bind to the corresponding ligands on the activated lymphocyte. And again there is an inhibition of the immune response.

If the tumor is not allowed to express these receptors, then the body's own immunity will begin to actively fight against cancer cells.

The first immuno-oncological preparations

A few years ago, drugs appeared – the so-called inhibitors of regulatory molecules of key stages of the immune response, which work exactly on this principle, removing the inhibition of the immune response.

In 2011, the first such drug for the treatment of metastatic melanoma was registered in Europe and the USA – an anti-CTLA4 monoclonal antibody. And in 2015, drugs for the treatment of end-stage lung cancer, melanoma and kidney (anti-PD1 monoclonal antibodies) were already registered.

In 2016, an anti-PDL1 drug (atezolizumab) was released, which received the status of "breakthrough therapy" from the FDA (US Food and Drug Administration) in the treatment of advanced bladder cancer and non-small cell lung cancer.

Enough time has passed since the beginning of clinical trials of these drugs to judge that they are really effective.

As Sergey Tyulyandin notes, when we talk about the metastatic process, the effect of chemotherapeutic drugs is quite short. But, if immuno-oncological drugs are used in this case, the effect will be much longer.

"For example, patients with metastatic melanoma, the most terrible and evil tumor, live at the expense of such drugs for up to 10 years. If someone had told me this five years ago, I would never have believed it," comments Sergey Tyulyandin.

What will happen in Russia

In the spring of 2016, for the first time, the immuno-oncological drug ipilimumab was registered in Russia. Atezolizumab and other immuno-oncological drugs are expected to be registered in 2017-2018.

But there is a big problem here. The fact is that, according to published data, unfortunately, immuno-oncological drugs are effective only for 20-30% of patients. It is still difficult to say why.

It is the question for which patients immuno-oncological therapy will be especially effective that Russian specialists are trying to answer. To this end, the Russian Society of Clinical Oncologists, the Russian Society of Pathologists, with the support of the immuno-oncological drug developer company, will develop uniform standards for testing patients for the need to use innovative immunotherapy.

It is worth adding here that such treatment, like all innovative therapy, is expensive. According to the chief physician of the city hospital No. 62 Anatoly Makhson, the cost of treatment of metastatic melanoma can reach up to 40 thousand euros per patient.

Obviously, this is not an easy story for Russia.

"Therefore, preparatory work is very important to debug diagnostic moments in order to answer the question of which patients will respond to treatment. The effect of these drugs is fantastic, but it is important to understand which patients, which drugs will act," says Sergey Tyulyandin.

Modern targeted immuno-oncological drugs are aimed at blocking the interaction of the PD-L1 ligand located on the tumor cell and the PD1 receptor located on the surface of the T cell. Therefore, before starting treatment, it is necessary to determine the presence of PD-L1 protein components, if there are many of them, then the tumor is protected from T cells, and new drugs are needed to break this connection, if not, then the probability that anti-PDL1 / PD1 drugs will be effective is lower.

Sergey Tyulyandin adds that the Russian Society of Clinical Oncologists has been developing a program of molecular genetic testing in oncology for a long time, and, moreover, outside the framework of state funding.

"We have met with the Ministry of Health more than once and talked about the fact that we have a network of such laboratories, there are trained doctors and specialists – just take them for funding. But this is a very difficult question – after all, if the methods of molecular genetic testing and morphological analysis of tumors are included in the treatment standards, then the state will be obliged to finance these costs. It has to happen. This is how the system works in all developed countries. But it is unclear when this will happen in Russia. We've been talking about this for five years now. The standards are written. They were sent to the Ministry of Health two years ago. But there is no movement yet," says Sergey Tyulyandin.

Portal "Eternal youth" http://vechnayamolodost.ru  25.08.2016

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