The latest research reveals: the switch that controls CAR-T cell therapy turns out to be a leukemia drug

Car-t cell therapy is known as a breakthrough in the treatment of some blood tumorsIt can transform patients' autoimmune cells into anti-cancer weaponsHowever, how to better control car-t cell-related acute side effect cytokine release syndrome is still a problem to be solved< br / > recently, a German research team found a possible solution in the Bristol Myers Squibb leukemia drug sprycel< br / > scientists at the University of Pittsburgh hospital say that sprycel can take effect quickly, temporarily stopping the activity of car-t cells in mice, so that animals can avoid the potentially fatal cytokine release syndromeThe results, published in the journal Science Translational Medicine, show that the drug can be used as a switch for car-t cell therapy< br / > cytokine release syndrome is caused by inflammatory molecules released by car-t cells and innate immune cellsAt present, the therapeutic methods that can be used to control cytokine release syndrome can neither completely control the function of car-t cells nor stop the process of anti-cancerCar-t cell immunotherapy has a significant response rate, but it often has serious toxic effects in the process of treatment, in which cytokine release syndrome is the most frequent and prominent acute adverse reactions, which can be life-threatening in serious cases< br / > car-t therapy contains CD8 + killer T cells and CD4 + helper T cellsIn the experiment, researchers at the University of wittsburgh hospital found that sprycel could block the two types of car-t cells by interfering with an enzyme called Lck, making them inactive, thus preventing them from producing inflammatory molecules that lead to the cytokine release syndromeAccording to the team, the blockade lasted for seven days and the patients did not show any other symptoms< br / > it is reported that sprycel is a second-generation tyrosine kinase inhibitor designed to help inhibit bcr-abl, an abnormal protein found on Philadelphia chromosome mutations in most patients with chronic myeloid leukemia (CML) and some patients with all, which can trigger the production of damaged or immature white blood cellsBy targeting bcr-abl protein, sprycel can reduce the number of damaged leukocytes in the body, thus producing more normal cellsIn the United States, sprycel was approved in January 2019 for the first-line treatment of Ph + all pediatric patients combined with chemotherapyThis approval also marks the second pediatric leukemia indication approved by sprycel in the United States, and makes it the first and only second-generation tyrosine kinase inhibitor for Ph + all pediatric patients< br / > can sprycel be reopened after it is closed? After carefully removing sprycel from the cell culture, the researchers found that car-t cells quickly began to work again and began to kill the target cells Within 7 hours, car-t cells have recovered their full anti-cancer attack ability when they decompose target cells, the study said < br / > Michael hudecek, senior author of the study, and colleagues compared the inhibitory effect of sprycel with dexamethasone, a steroid commonly used to control car-t cells through systemic immunosuppression The results of the comparative test showed that sprycel could stop car-t activity immediately and completely, while dexamethasone had a relatively slow action and only showed partial inhibition < br / > to test these findings, the German team also used lymphoma mice as experimental models The team found that rapid administration of sprycel to a subpopulation of mice after car-t infusion prevented 70% of the mice from dying of the cytokine release syndrome, while only 25% of the untreated mice survived in the cytokine release syndrome After the termination of sprycel, car-t cells in mice also recovered rapidly, showing anti lymphoma activity < br / > at present, scientists are studying the therapeutic potential of car-t in blood cancer, so it is very important to effectively control the complications that may endanger life Researchers led by the University of Southern California recently used a chimeric antigen receptor variant that they believe produces low levels of cytokines Researchers from sanraffaele hospital in Italy and memorial Sloan Kettering in New York found that the treatment of kineret for rheumatoid arthritis developed by Amgen may be an effective way to control cytokine release syndrome < br / > at present, sprycel can be used as a good first aid drug to quickly close the risk of cytokine release syndrome in patients receiving car-t infusion In the study, hudecek's team said that the drug's rapid onset and complete but reversible control of car-t cells made it an attractive treatment option, because in many clinical cases, patients with cytokine release syndrome are only transient < br / > more importantly, the use of sprycel within a specified time interval may also play a second role: to protect car-t cells from loss of aggression When cells participate in the chronic signal transduction, it will lead to car-t cell fatigue, thus limiting or reducing the killing ability of cancer cells Researchers say Sprycel can prevent T cell failure by giving cells a short rest < br / > reference link: press the pause button on car-t cells with Bristol myers'leukemia plug