Scientists from Kazan Federal University (KFU) have created a technique that will reduce the risk of dangerous side effects during car-T cell oncotherapy. With this treatment, the tumor is destroyed by the person's own lymphocytes - for this, they are first taken from the patient, genetically edited so that they attack the tumor tissue, and injected back into the body. These modified lymphocytes are called CAR-T cells. The researchers also found out against which types of tumors such therapy can be effective. This was reported to RT in the press service of the Ministry of Education and Science. The results are published in the journal Biomedicines.
CAR-T therapy acts on the tumor selectively, unlike chemotherapy, which destroys healthy tissues. However, this therapeutic technique also has serious risks. The fact is that some patients may develop too violent a reaction of the immune system - a cytokine storm, which can lead to the death of a person. Today, the world is looking for ways to either stop the cytokine storm with CAR-T therapy, or predict the likelihood of such a reaction in a particular patient.
The authors of the work printed on a bioprinter a tumor model of living cancer cells and added CAR-T lymphocytes to it. Scientists have traced the process of lymphocyte release of cytokines - molecules that enhance antitumor activity, but can also cause a cytokine storm. It turned out that the increase in the concentration of cytokines increased the activity with which lymphocytes attacked cancer cells.
"We analyzed the environment in which the cells were incubated and found that on about the fifth day of interaction between CAR-T and tumor cells, the peak level of pro-inflammatory cytokines reaches a peak. At the same time, the maximum antitumor effect of CAR-T cells was observed. Thus, the higher the level of cytokines, the more aggressive car-T cells behaved against tumor cells and destroyed them faster, "aigul Valiullina, a researcher at the Industrial Biopharmaceuticals Research Laboratory of the Institute of Fundamental Medicine and Biology of KFU, Candidate of Biological Sciences, explained to RT.
- Image of cancer cells
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According to scientists, the laboratory model can be used to assess the risk of a cytokine storm during therapy. To do this, it is enough to place car-T cells and cancer cells of a particular patient in one "tube", and then measure the level of cytokine production in this model. Too rapid production of cytokines will indicate a high risk of cytokine storm in the patient. In this case, doctors will be able to choose the appropriate treatment program in advance, eliminating possible side effects.
"This approach has no analogues yet. Therefore, we hope that in the future it will be finalized and will find its application in clinical practice in CAR-T therapy of patients with both hematological and solid tumors (developed not from cells of the hematopoietic system, but in tissues and organs. — RT)", — said in an interview with RT the scientific director of the project, the head of the Research Laboratory "Industrial Biopharmaceuticals" of KFU Emil Bulatov.
Scientists intend to refine and implement the technique in clinical practice together with Russian cancer centers and biopharmaceutical companies.
In addition, the researchers found that CAR-T cells are able to overcome the protective systems of malignant tumors. The fact is that tumor tissues at the biochemical level are masked from the immune system. And solid tumors, which did not develop from cells of the hematopoietic systems, also surround themselves with molecules that act as a barrier in the way of immune cells. The authors of the work found that CAR-T cells are able to penetrate into a dense tumor microenvironment and destroy malignant neoplasms. This proves that CAR-T therapy can be effective not only against oncological diseases of the blood and lymphomas, but also against solid tumors, experts say.