Advanced CAR-T
Russian scientists have figured out how to destroy cancer more effectively
Scientists from the Institute of Bioorganic Chemistry named after Shemyakin and Ovchinnikov of the Russian Academy of Sciences, the Institute of Chemical Biology and Fundamental Biology of the Siberian Branch of the Russian Academy of Sciences, together with specialists from the Scripps Institute (USA), with the participation of Pharmsintez, have developed a technology to improve the effectiveness of treatment of patients with B-cell lymphoma, an aggressive form of cancer of the lymphatic system.
Representatives of the Russian team of developers explained to RIA Novosti that the new approach is based on the so-called CAR-T therapy (from the English chemegis antigen receptor), which allows treating the patient with the help of his own immune system cells – T-lymphocytes. These cells are isolated from the patient's blood, and then, with the help of genetic engineering, they are "reprogrammed" in such a way as to effectively recognize tumor cells and destroy them.
It is fundamentally important that the patient gets his own T-cells back. Therefore, they do not die, but are carried by blood through the organs and tissues of the patient and come into contact with tumor cells. Moreover, they are able to reproduce themselves in the spleen and lymph nodes. In 2013, one of the world's leading scientific journals Science named CAR-T therapy the breakthrough of the year in immunotherapy.
CAR-T technologies have been recognized as one of the most effective methods of combating severe forms of cancer. The most famous example of the use of this type of therapy was the drug Kimraya (tisagenlekleysel) developed and approved in the USA for the treatment of acute B-cell lymphocytic leukemia and B-large cell lymphoma.
An improved approach
Cells of malignant tumors of the lymphatic system usually carry characteristic proteins (so-called antigens) CD19 and CD20 on their surface. They are the "target" in the treatment with the drug Kimraya. But since some healthy cells also have these antigens, they also die when using CAR-T technology. In addition, the weak point of this method is that during treatment, altered cells may appear in the tumor without CD19 and CD20 molecules, which "hide" from attack by CAR-T cells.
As representatives of the Russian team of authors noted, their approach solves this problem. The principal difference of the improved method is that it allows you to identify the unique antigens of a particular patient, determine the sequence of the gene that encodes them, and then in exactly the same way as in the classical CAR-T technology, "reprogram" T-lymphocytes. They will carry an artificial antigenic receptor, specifically, as a key to the lock corresponding to the antigen on the surface of the patient's tumor cells. As a result, tumor cells themselves recognize therapeutic CAR-T cells and start their own destruction. The results of this work are published in the prestigious international journal Science Advances.
A key feature of the developed technology may be a new standard for the safety and effectiveness of CAR-T therapy, said Academician Alexander Gabibov, Director of the Institute of Bioorganic Chemistry, who led the development.
The work was carried out with the support of the Russian Science Foundation. The team of researchers from the Scripps Institute was led by one of the world's leading scientists in the field of biomedicine, Professor Richard Lerner.
Who participated in the opening
The M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences is the largest center of physico–chemical biology and biotechnology in Russia. The Institute heads the ongoing work in Russia related to the chemical study of living matter. The Institute conducts research on the molecular mechanisms of various life processes, their practical use in the interests of medicine and agriculture, and also develops fundamental and applied aspects of biotechnology.
The Scripps Research Institute is one of the world's largest non-profit research institutes engaged in biomedical science. The Institute has created eight medicines previously approved for use by the U.S. Food and Drug Administration.
The company "Pharmsintez" is engaged in the development and production of pharmaceutical substances and medicines both in its own portfolio and on the terms of contract production. This is the first Russian biopharmaceutical company that entered the public stock market in 2010 and has innovative drugs in its portfolio with a high potential for commercialization in the US and EU markets.
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