Revealing death receptor signaling is essential for CAR-T cell therapy

  Clarifying death receptor signaling is essential for CAR-T cell therapy\nScientists have found ways to enhance CAR-T cell therapy. In a new study, researchers from research institutions such as the University of Helsinki in Finland said that drug analysis and CRISPR-Cas9 gene editing have opened up new ways to develop CAR-T cell therapies for the treatment of leukemia and lymphoma.

  This study investigated the effects of more than 500 anticancer agents on CAR-T cell function. CAR-T cell therapy has achieved excellent effects on certain blood cancers and lymphomas that are resistant to other therapies. In CAR-T cell therapy, the patient's own T cells (a type of immune cell) are extracted from the blood and genetically modified to express chimeric antigen receptors (CAR) in order to recognize them. And it destroys cancer cells. The corresponding author of this paper, Professor Satu Mustjoki of the University of Helsinki, said: "Although the treatment is very effective, CAR-T cell therapy is not effective for all patients. It can also cause adverse reactions."

  This kind of drug analysis focused on one kind. A class of drugs called SMAC mimics can make cancer cells sensitive to CAR-T cells in laboratory tests. At the same time, the study also found that drugs that block CAR-T cell function can treat adverse reactions caused by CAR-T cell therapy. by using

  CRISPR gene editing method, these researchers studied the mechanism that affects the sensitivity of cancer cells to CAR-T cells. They found that a process called death receptor signal transduction and the FADD gene required to initiate the process are important for CAR-T cell function. This CRISPR gene editing method also revealed that the mechanism of action of the SMAC mimic is based on the activation of death receptor signals. According to the test results, SMAC mimics can be used to further sensitize cancer cells to cell death caused by CAR-T cells. If further research supports the drug prospects identified in this preliminary analysis, SMAC mimics can be used to improve the effectiveness of CAR-ΔT cell therapy.

  The lead author of the paper, PhD student Olli Dufva at the University of Helsinki, said: "This study provides a large amount of data on the effects of anticancer drugs on T cell function. These data may be useful for the development of anticancer drugs and treatments that activate the immune system. "