Smart immunotherapy
CAR-T therapy is the most promising method of treatment of immunotherapy of oncological diseases. It is based on the use of genetically modified T-killer lymphocytes synthesizing chimeric antigen receptor (CAR) and attacking cancer cells. However, the number and intensity of side effects, up to fatal, significantly limits its use. A group of scientists led by Wilson Wong from Boston University were able to make CAR-T therapy safer and more effective.
Traditional immunotherapy CAR-T uses altered lymphocytes to destroy a specific type of cancer cells in a particular patient's body. The new improved system, called SUPRA-CAR-T by the authors (from the English split, universal and programmable – shared, universal and programmable), can be targeted at different types of cancer cells, enabled or, if necessary, disabled and gives significantly better results than similar methods used and being developed now.
Immunotherapy is accompanied by pronounced side effects. Methods of drug treatment have been developed that block the unwanted immune response, preserving only the antitumor effect. The SUPRA CAR-T system allows you to completely disable therapy if undesirable effects threaten your health or cannot be eliminated.
The concept of SUPRA CAR-T is slightly different from traditional immunotherapy. If CAR-T is the creation of killer cells tuned against a tumor, then SUPRA CAR-T is primarily an antibody that carries T-killers with it.
Normally, the immune system is activated only if a foreign agent sends a double signal, which is picked up by lymphocytes and activates them. SUPRA CAR-T, unlike the traditional "single-signal" CAR-T, works the same way. Before attacking a tumor, the T-killer must make sure that both targets are present in the target cell. If there is only one target, the system will remain inactive.
SUPRA CAR-T cells can be "disconnected" at any time and redirected to another target: T-killers, if necessary, detach from the antibody. The ability to change the target in the future will help to fight relapses, the fight against which is complicated by the fact that cancer cells are constantly mutating, trying to survive in antitumor therapy. SUPRA CAR-T does not require constantly creating new T-lymphocytes. By the way, this process is the most expensive part of the entire course. When using a new mtod, it is enough to introduce a new portion of antibodies for effective treatment.
Another feature of modified therapy is its safety. By introducing a third component, the system can be weakened: it interacts with the antibody, displacing T-killers. This will be necessary if the severity of side effects becomes threatening to the health and life of the patient. The level of deactivation can be adjusted up to a complete shutdown.
The authors hope that the described changes will help make immunotherapy cheaper, safer and more effective. In the future, they plan to program the system so that cells can synthesize the necessary proteins themselves, for example, to destroy the dense shell of cancer cells.
Article by J. H. Cho et al. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses is published in the journal Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of BU: Upgrading the Immune System to Fight Cancer.