It is possible to “switch on” or “turn off” immune cells that have been designed to fight cancer.

There are billions of immune cells that help defend us from diseases, and while they are capable of incredible things, they occasionally require a little help. Since the 1970s, medical researchers have been attempting to reverse-engineer living immune cells in order to develop therapies that are more effective against aggressive diseases such as cancer.

CAR T-cell therapy is a treatment that includes changing immune cells called T cells, which are microscopic powerhouses that take on infections. This treatment is one of the most significant and relatively recent advancements in the fight against cancer. Researchers have devised a strategy that involves removing T cells from a patient’s blood, inserting a unique type of gene known as a receptor, which binds to cancer cells, and then returning the patient’s blood with the T cells that have been genetically modified. Chimeric antigen receptors, often known as CARs, are a type of receptor that can be modified so that they precisely match the type of cancer that is being treated. In particular, leukaemia is one of the cancers that has been shown to respond well to treatment with CARs. When CAR-T cells are reintroduced into the circulatory system, they immediately begin to proliferate and engage in the battle against cancer.

CAR-T cells have the potential to overstimulate the immune system, which can result in the discharge of a chemical compound known as cytokine. Cytokine release syndrome is an inflammatory disorder that has the potential to be fatal if it is brought on by this. Other major consequences can include issues with the nervous system, as well as other organs in the body being targeted in error by the immune cells.

Wong and a group of other researchers are aiming to incorporate a safety switch into the design of the CAR-T cells, which will reduce the amount of risk that patients face while undergoing this innovative treatment. It is now possible to prevent cells from activating and causing severe side effects by using a novel form of CAR-T cell that can be switched on or off. The findings of this research were published in a recent article in the journal Cancer Cell.

Their brand innovative method is known as the VIPER CAR-T cells. VIPER cells, which are created such that they may be controlled by giving a patient an antiviral medicine that interrupts the cell’s function, minimise the safety issues that are associated with regular CARs. VIPER is an acronym that stands for Versatile ProtEase Regulatable cells.

Part of the receptor protrudes through the cell membrane of every CAR-T cell, whereas other parts of the receptor are located within the cell. The portion that extends beyond the membrane forms interactions with cancer antigens, which ultimately leads to the activation of the T cell and the destruction of the cancer cell. In VIPER CAR-T cells, a unique protein chain has been introduced in the space close to the receptor. The researchers developed two distinct systems: one that is activated at the moment when the VIPER CARs are transferred back to a patient, and another that is deactivated during this process. Although the two systems operate somewhat differently, it is possible for a patient to turn either one off or on by taking a medicine that has been licenced by the FDA and is commonly employed in the treatment of hepatitis C.

John T. Ngo, an assistant professor of biomedical engineering in the ENG department, and Ahmad S. Khalil, an associate professor of biomedical engineering in the ENG department who is also the associate director of the Biological Design Center, were also members of the research team. Other CAR-T cell systems that are controlled by medicines have been constructed by scientists, but this is the first system that has two modes of operation—on or off. According to Wong, the two modes will make it possible for physicians to target the cancer in a more aggressive manner, as it will be possible to dial down the treatment if it becomes required. Alternately, in the event that there is any room for doubt, medical professionals could gradually activate the VIPER CAR-T cells.

At this point, the research has only been conducted in cell cultures and mice. And to further verify the efficacy of their method, the research team compared their findings to those of other studies that had taken a similar strategy. They discovered that VIPER CAR-T cells performed better than other methods. They also employed VIPER in conjunction with other types of CARs within the same T cell, which means that the T cell was created to include two separate cancer-fighting receptors. According to Wong, this could make it possible for modified T cells to target two distinct disease markers at the same time, which would open the door to even further improvements in cancer gene therapy.

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