A relatively recent advance in the fight against cancer has been the creation of CAR-T cell therapy, a treatment that involves modifying immune system cells known as T cells. Scientists have discovered a way to remove T cells from an individual’s blood, insert a special type of gene called a receptor that binds to cancer cells, and transfer these cells back to the patient.
This CAR receptor, which stands for “Chimeric Antigen Receptor”, is tailored to match the specific cancer being targeted and has been found to be effective in treating certain types of cancer, especially leukemia. Once CAR-T cells re-enter the bloodstream, they begin to replicate and begin their fight.
“It’s a very exciting technology,” says Wilson Wong, an associate professor of biomedical engineering at the Boston University School of Engineering, who has studied CAR-T cells for more than 10 years. But he admits there are safety issues that can make therapy extremely risky.
It is that CAT-T cells can overstimulate the immune system, which triggers the release of a substance called a cytokine. This can cause a potentially fatal inflammatory condition known as cytokine release syndrome. Other serious complications can include neurological difficulties or other organs in the body being mistakenly targeted by the cells.
And that’s where the novelty of this treatment comes in. To make CAR-T cell therapy less risky for patients, Wong and a team of researchers are working to create a safety switch built into the CAR-T cell design. In a new paper in Cancer Cell, researchers reveal a new type of CAR-T cell that can be turned on or off, making it possible to stop cells from activating before serious side effects occur.
This new system creates cells designed to be controlled, and is called VIPER – Versatile ProtEase Regulatable. CAR-T VIPER cells can be “deactivated” by administering an antiviral drug to the patient, which stops their activity. Thus, safety issues related to traditional CAR cells are reduced. “We see this as the next generation of this type of therapy,” says Wong.
All CAR-T cells have part of the receptor on the outside of the cell membrane, while part of it is inside the cell. The part on the outside of the membrane binds to cancer antigens, which activates the T cell and destroys the cancer cell.
VIPER CAR-T cells have a special protein chain inserted close to the receptor. Two different types of systems were created by the researchers. One that turns on when VIPER CARs are transferred back to the patient, and one that turns off. Both work in slightly different ways, but they can be turned on or off by the patient when taking a drug that is commonly used to treat hepatitis C.
“That’s the most exciting part of this study, that antivirals have already been approved by the FDA,” says Huishan Li, the paper’s lead author and a postdoctoral fellow in Wong’s lab and at the Khalil Lab. When administered, the drug molecule interacts with the inserted protein chain, initiating a series of reactions in the cell to make it disengage or activate, depending on which system is being used.
For now, this work has been done in cell cultures and mice. And to further test their approach, the research team compared their results with other similar studies, finding that VIPER CAR-T cells outperformed other systems.
They also used VIPER alongside other types of CARs within the same T cell – that is, the T cell was engineered with two different cancer-fighting receptors. This could allow the engineered T cells to target two different cancer markers at the same time, says Wong, opening the door to even more advances in cancer gene therapy.
Via Medical Express
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