New CAR-T Cell System Offers On-Off Capability For Safer, More Effective Cancer Therapy

Biomedical engineers at Boston University have developed a new system that could enable more potent use of CAR-T cells in the fight against cancer.

Cancer News

CAR T-cell therapy is a relatively new major advancement in the battle against cancer. It is a result of many years of research by scientists to find a way to recruit immune cells to combat cancer and other damaging disorders. Serious adverse effects may result from the therapy, however.

Read Also: Researchers Say Cancer Immunotherapy Could Get a Boost from Reinvigorating Extremely Exhausted T Cells

This new system that is being worked on looks to make the use of CAR-T cells for cancer therapy safer and more effective. With this new form of immunotherapy, drugs can be used to turn immune cells on or off. This would make it easier for physicians to safely tailor treatment to individual patients.

“It is a very exciting technology,” said Wilson Wong, Ph.D., an associate professor of biomedical engineering at Boston University College of Engineering. “We see this as the next generation of this type of therapy.”

Wong has over a decade of experience in the study of CAR-T cells. The knowledge he has garnered so far was brought to bear in this research.

The new CAR-T cell system developed by Wong’s team was revealed in a paper published in Cancer Cell.

CAR-T cells for protection

T cells are a type of white blood cell that aid in defending the body against invading pathogens. Scientists can modify them to target and destroy cancer cells. CAR T-cell therapy involves employing such modified T cells to fight infections and diseases.

Researchers have worked out a means of extracting T cells from an individual’s blood and engineering them by inserting a special gene known as a receptor. They can then re-introduce the engineered T cells back into the person’s body.

The receptor involved is called a chimeric antigen receptor (CAR). It is modified to match that particular cancer that is to be targeted. The engineered T cells begin to replicate when they enter the bloodstream and start to wage war against cancer.

CAR T-cell therapy has been proven to be helpful for the treatment of some cancer forms. Available evidence suggests that it is effective for leukemia treatment in particular.

However, there is a problem. CAR-T cells can overstimulate the immune system in some cases. This can lead to higher cytokine levels, with a potential for awful complications.

Increased cytokine release can result in cytokine release syndrome, an inflammatory condition that could become fatal. Neurological problems and unintentional organ targeting by immune cells are also potential issues.

Wong and his colleagues wanted to reduce the chances of these possible complications from CAR T-cell therapy.

Read Also: Chemo-Immunotherapy Combination Shows Promise Against Pancreatic Cancer in New Study

A safer system

These researchers are working on what they call VIPER CAR-T cells. VIPER is an acronym for Versatile ProtEase Regulatable.

The improved CAR-T cells are designed to allow for turning on or off. The new system will come with a built-in safety switch that can be controlled using an antiviral drug.  This would allow for the cells to be blocked from activating, when necessary, to minimize the risk of serious side effects.

VIPER CAR-T cells have a portion of their receptor sticking out of the cell membrane while the other resides inside the cell. The part outside the membrane attaches to cancer antigens, thus activating the T cell and killing the cancer cell.

The scientists created two different systems that function slightly differently. One system is turned on when the engineered T cells are transferred into a patient while the other is turned off. However, both systems can be switched on or off with the use of an FDA-approved hepatitis C drug.

The medication interacts with a special protein chain, which researchers inserted beside the receptor when taken by a patient. This sets off a chain of reactions inside a cell that either turns the cell on or off.

According to the researchers, this is the first CAR-T cell system to feature two modes (on and off). Other CAR-T cell systems that are controlled with drugs offer only one mode.

The two-mode design of this new system will put doctors in better control when targeting cancer cells. It gives the freedom to go aggressive on cancer or tone things down, based on a patient’s condition.

Researchers compared VIPER CAR-T cells with other systems and found they performed better. They said the cells could be used to target more than two cancer markers at the same time, having been engineered with two distinct cancer-fighting receptors.

Read Also: Solid Tumor Destruction: A Possible Breakthrough with Car T Cell Immunotherapy

However, this technology is not ready for human use in clinical settings – that is a target for the future. The team carried out its research in cell cultures and mice. It is still working to fine-tune the system in the lab before applying it to humans.


High-performance multiplex drug-gated CAR circuits



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