Billions of immunities that help protect us from disease Cells are indeed amazing things, but sometimes they need a little push. For decades, scientists have struggled to find ways to engineer living immune cells to better fight aggressive diseases such as cancer.
A relatively recent major advance in the fight against cancer is CAR T-cell therapy, a therapy that involves modifying immune cells. The therapy is called T cells, microscopic cells that can withstand infection. Scientists have found a way to remove T cells from a person’s blood, inserting a special gene called a receptor that binds to cancer cells and transfers the engineered T cells back into the patient. This type of receptor—a chimeric antigen receptor, or CAR—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 the CAR-T cells re-enter the bloodstream, they begin to replicate and start fighting.
“This is a very exciting technology,” said Wilson Wong, associate professor of biomedical engineering in Boston University’s School of Engineering. He has been engaged in CAR-T cell research for over 10 years. But he said there are safety concerns that make the treatment extremely risky.
Sometimes, CAR-T cells can overstimulate the immune system, triggering the release of substances called cytokines. This can lead to a potentially fatal inflammatory condition called cytokine release syndrome. Other serious complications can include neurological disorders, or other organs in the body being wrongly targeted by immune cells.
To reduce the risk to patients of this groundbreaking therapy, Wong and a team of researchers are working to create a CAR built into the – T cell design. In a new paper from Cancer Cell, researchers reveal a new type of CAR-T cell , which can be turned on or off, preventing cell activation before serious side effects occur.
Their new system is called VIPER CAR-T cells. VIPER (stands for Versatile ProtEase Regulatable) cells are engineered so they can be controlled by giving patients an antiviral drug that disrupts cell activity, reducing the safety concerns posed by traditional CARs.
“We think this is the next generation of this therapy,” Wong said.
In all CAR-T cells, part of the receptor extends outside the cell membrane and part is inside the cell membrane. cell. Parts that adhere to the outside of the membrane bind to cancer antigens, which then activate T cells and destroy cancer cells. VIPER CAR-T cells insert a special protein chain next to the receptor. The researchers created two different systems—one that turns on when the VIPER CAR is transferred back to the patient, and one that turns off. The two systems work slightly differently, but can be turned off or on by patients taking FDA-approved drugs commonly used to treat hepatitis C.
“This is the most exciting part of this study, the antiviral drug has been approved by the FDA,” the paper said lead author Huishan Li, a postdoc in Wong’s lab and Khalil’s lab. When administered, the drug molecule interacts with the inserted protein chain, triggering a series of reactions in the cell that disengage or activate it, depending on the system used.
The research team includes ENG Assistant Professor of Biomedical Engineering John T. Ngo and ENG Engineer Ahmad S. Khalil Associate Professor of Biomedical Engineering, Deputy Director of Biodesign Center. Scientists have made other drug-controlled CAR-T cell systems, but this is the first with two modes of operation—on or off. The two modalities could allow doctors to target cancer more aggressively because less treatment can be given if necessary, Wong said. Alternatively, doctors can gradually turn on VIPER CAR-T cells if there is any uncertainty.
Currently, this work is done in cell cultures and mice. To further test their approach, the team compared their results with other similar studies and found that VIPER CAR-T cells outperformed other systems. They also used VIPER and other types of CARs in the same T cells — meaning, the T cells were designed with two different cancer-fighting receptors. This could enable engineered T cells to simultaneously target two different cancer markers, Wong said, opening the door to further advances in cancer gene therapy.
“Not only do we have security controls, we can have multiple versions at the same time,” Wong said. Having perfected the technology in the lab, the team’s long-term goal is to apply the technology to humans in clinical settings.
More information: Huishan Li et al., High-Performance Multiplex Drug-Gated CAR Circuits, Cancer Cells
(2022). DOI: 10.1016/j.ccell.2022.08.008
Citation : Immune cells engineered to fight cancer Can be “on” or “off” (September 10, 2022) Retrieved September 22, 2022 from https://medicalxpress.com/news/2022-09-immune-cells-cancer.html
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