FDA first approved gene therapy for the treatment of leukemia.

On August 30, 2017, Kymriah, based on genetic modification of the patient's own cells, received approval from the FDA. Now in the United States, children and adolescents with acute lymphoblastic leukemia can receive treatment with genetically modified lymphocytes, the so-called CAR-T cells.

Kymriah was developed by the Swiss biotechnology company Novartis. The cost of the course (single injection) of Kymriah gene therapy is 475 thousand dollars.

FDA approval is a historic event for the United States and other countries. Prior to this, DNA editing technologies were used to treat cancer only in the framework of scientific experiments and clinical studies. Today permission has received the finished product.

Solo Atlas project experts tell us how Kymriah works and what this decision means for each of us.

T-cell kills tumor leukocyte

When does Kymriah technology apply?

Therapy is used to treat B-cell acute lymphoblastic leukemia after a repeated relapse or in the absence of a response to standard treatment. This is a cancer of the blood and bone marrow, as a result of which the body produces too many white blood cells - B-lymphocytes. At the same time, the structure of such leukocytes is impaired, and they cannot perform their functions: recognize infections, produce antibodies, and regulate immunity.

Acute lymphoblastic leukemia is the most common type of malignancy in children 4–7 years old. It can occur as a result of random genetic mutations, some hereditary diseases, and exposure to radiation.

One of the methods of treatment today is bone marrow transplantation. Finding the right donor is usually a big problem, and the transplantation does not guarantee recovery.

How it works

Kymriah - personalized gene therapy. A patient takes a sample of his own T-lymphocytes (these are the cells responsible for fighting against tumors in the body) and implant in them a genetic construct based on a harmless virus. Such genetically modified cells are grown (multiplied) under special conditions and the finished product is injected back into the patient's body. It is planned that the whole process will take an average of 22 days: from blood sampling to the introduction of Kymriah.

Genetically modified T-lymphocytes contain a new protein - the chimeric antigen receptor (chimeric antigen receptor or CAR), which helps them find and target destroying dangerous B-lymphocytes.

Kymriah method is valid only for those types of leukemia, in which the work of B-lymphocytes is impaired. These include 15% —20% of all cases of acute lymphoblastic leukemia.

What are the side effects

The use of therapy can cause serious side effects - cytokine release syndrome, fever, neurological complications. This is due to the fact that along with the "cancerous" B-lymphocytes during treatment, healthy lymphocytes also die.

To reduce the risk of side effects, along with Kymriah technology, the FDA administration has extended a license for Actemra, which alleviates the symptoms of cytokine release syndrome. Another precaution is the mandatory certification of clinics that will work with Kymriah technology.

What does this industry solution mean?

Vladislav Mileyko, CEO of Atlas Onco Diagnostic:

“Currently, dozens of companies and research groups are developing CAR-T cellular drugs for the treatment of cancer. This is probably the most complex technology of medicinal treatment, as it has grown at the interface of cell biology, genetic engineering and molecular oncology. Developers need to address several fundamental issues on the way to creating the drug: which chimeric antigen to use for selective targeting of tumor cells, how to perform genetic modification of lymphocytes, and most importantly, how to ensure reliable and scalable operation of the entire technology assembly.

So far, the greatest progress has been achieved precisely in hematological tumors, where it is relatively easy to determine the “enemy image” - specific protein molecules on the surface of tumor cells, against which modified CAR-T cells should be directed. There are more difficult challenges ahead - the therapy of solid tumors, in which the molecular profiles are much more diverse, and the tumors themselves are able to successfully avoid the attack of T-lymphocytes.

Of great importance is the interest of big pharma and the recognition of the new technology by the regulator. This will be able to advance not only the industry, but also give a new impetus to scientific developments in the most advanced areas, such as immunotherapy, genome editing and, of course, molecular diagnostics. ”

Source: https://habr.com/ru/post/406347/

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