CAR-T cells with RK motif are more lethal to cancer cells

  In the immune system, the role of T cells is to destroy infected cancer cells. For this, you need to be aware of threats. It is believed that foreign molecules (so-called antigens) bind to T cell receptors (TCR) on the surface of T cells. Now, in a new study, researchers from Freiburg and Bayreuth in Germany have successfully demonstrated how this cognitive mechanism activates T cells and converts them into attack mode. T cell receptors are small machines made up of many single proteins. Once the infected cells and tumor cells in the body are identified, the so-called lymphocyte-specific kinase binds to the newly discovered RK-motif T cell receptor. This combination opens up T cell receptors and activates T cells to become killer cells, eliminating the threat. Minge commented on this discovery: "To my surprise, this RK motif has never been explained. Immunologists have been studying T cell receptors for more than 30 years."

  These findings help to build a bridge between threat recognition and immune response activation at the molecular level, which reveals the basic operating principles of the immune system. T cells perform multiple functions. When the body's own cells pose a threat to the human body, cytotoxic T cells (also called killer cells) are particularly responsible for destroying them. This is because you are infected with bacteria and viruses. Because they are cancer cells. T cells specifically recognize antigens on the cell surface and release toxic substances to destroy these target cells. In immunotherapy for cancer, doctors try to enhance this ability of the immune system. The University of Freiburg Medical Center has successfully used CAR-T cell therapy to treat patients, in which patient-derived T cells express artificial receptors (so-called chimeric antigen receptors, CAR) synthesized in the laboratory. I will be able to do it. , To specifically kill cancer cells in the same patient. In preclinical studies, these researchers found that CAR-T cells with an RK pattern can destroy cancer cells better than T cells without the pattern. These researchers discovered the RK motif by combining biochemistry, synthetic biology and immunology. They found that the RK motif is usually hidden to prevent harmful T cell activation and only exposed after binding to the antigen. This may explain why the RK motif has not been discovered before. Biochemical analysis allows them to understand this molecular signal in detail, and its immunological understanding and medical applications can explain its function in the body.

  Minguet explained: "This discovery gives us more control over T cells. Today, this is the only cell type that uses this new activation mechanism, so it can be done very specifically. In the future, this will not only help treat cancer, It can also improve the treatment of autoimmune diseases and immunodeficiency.