Stopcock for immunotherapy
Immunotherapy, unlike chemotherapy and radiotherapy, targets the body's immune system to attack cancer cells. In recent years, it has proved to be an extremely successful method of treating leukemias, lymphomas and other oncological diseases present in body fluids.
Therapy with genetically modified lymphocytes with chimeric antigen receptors (CAR-T) consists in taking the patient's T cells and injecting them into the blood after genetic modification, which gives them the ability to recognize and attack cancer cells. However, modified T-lymphocytes targeted at the tumor can also affect healthy tissues. This causes the toxicity of therapy, leading to damage to vital organs and even death.
A group of Swiss researchers from the Federal Polytechnic School of Lausanne (EPFL), the Cancer Research Institute named after Ludwig at the University of Lausanne (UNIL) and the University Hospital of Lausanne (CHUV) has developed a new method of disabling modified T-lymphocytes on demand – a kind of emergency system for patients who are not well tolerated treatment. The STOP-CAR control system was tested on mice that were injected with prostate cancer cells.
At the first stages, it works in much the same way as classical CAR-T therapy: T-lymphocytes are taken from the blood, they are genetically modified so that chimeric antigenic receptors are synthesized on the surface. These receptors allow the T-lymphocyte to recognize and bind to cancer cells. Then a signal is generated calling the cell to attack.
At this stage, differences appear. The researchers transformed the receptors on immune cells so that the signal generated by binding to antigens could be turned off.
The STOP-CAR control system includes the introduction of a molecule to the patient in the form of a separate drug that disrupts the interaction between T-lymphocyte receptors and proteins on the surface of cancer cells, thereby effectively disabling the T-cell.
The main advantage of STOP-CAR is that it is possible to turn on the T-lymphocyte again, for this you need to stop injecting the stop molecule.
In addition, observations have shown that prolonged exposure to antigens can cause depletion of T-lymphocytes. Turning off the cells for a while gives them the opportunity to "rest" and recuperate.
The development of the STOP-CAR system can accelerate the widespread introduction into clinical practice of CAR-T therapy, which is now considered too risky, for the treatment of various types of oncological diseases.
Article G.Giordano-Attianese et al. A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy published in the journal Nature Biotechnology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EPFL materials: Designing an emergency stop switch for immunotherapies.