CAR-T against tumors
Pilot preclinical tests of CAR-T lymphocytes on animals were carried out
Center for Personalized Medicine
The development of medicines in the modern world involves a long process, including mandatory stages of preclinical testing and production scaling, a strict quality control system of the product is created and observed. All these stages significantly exceed in time, labor costs, intellectual investments and financial needs the initial receipt of the test laboratory sample of the future drug. In their experimental studies of human diseases, scientists use animal models that require appropriate organization of animal maintenance, the approval of an ethical committee and detailed research protocols.
A promising area of translational medicine is the development of biomedical cell products, i.e. products derived from modified human donor cells. Preclinical research of such products is a complex organizational and scientific process. Currently, among biomedical cell products, one of the most promising approaches in antitumor therapy is CAR-T-cell therapy. It consists in the fact that T-lymphocytes are isolated from human blood, multiplied to a large number, genetically modified so that they "learn to recognize" tumor cells using special proteins on the surface (CAR), and then the resulting CAR-T cells are returned to the patient by infusion. Such "trained" cells independently find and destroy the tumor.
At the end of 2020, on the basis of the Almazov NMIC, within the framework of the NCMU "Personalized Medicine", scientists conducted a pilot experiment in which they searched for mechanisms of tumor resistance to immunotherapy, and also prepared models for further preclinical studies of CAR-T.
A non-standard approach was used in the work. Using the methods of molecular biology and genetic engineering, scientists injected CD19 antigen (a target protein on the surface of some oncological diseases) synthesized in this way de novo into the cells of a widely used model solid tumor, after which they tracked the growth and regression of the neoplasm, and also obtained additional data on the ability of SAR-T cells to penetrate tumor tissue. Thanks to various tests using laboratory animals, specialists were able to evaluate the effectiveness and toxicity of the obtained CAR-T, it was possible to choose the optimal effective method of administration, dosage regimen (from 250 thousand to 5 million cells per individual), as well as the required duration of therapy exposure (from 12 days to 1 month).
During the experiments, positive dynamics was recorded 12 days after the start of therapy, and the degree of immune response was determined at the minimum dosage of CAR-T. Animals even with huge neoplasms relative to their bodies with CAR-T cells injected once conditionally "recovered": after about a month, the neoplasm completely disappeared.
In addition to CAR-T targeted against the key antigen of tumor B lymphocytes - CD19, scientists are also actively investigating the functions of CAR–T cells to CD20 and NKG2D receptors, which in the future will open the way for the therapy of a wide range of oncological diseases and diseases of an infectious nature.
The work performed by the scientists of the NCMU "Personalized Medicine" today indicates the prospects and high probability of success in conducting further full-scale preclinical and clinical trials scheduled for 2021.
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