Cell: 'Remote Control' CAR-T Cells Make Cancer Immunotherapy Safer

Cancer treatments that use a patient's own genetically modified immune cells to attack cancer cells are safer and more effective if they can be switched on and off with an oral drug, according to a recent study in mice published in Stanford Medici.

The original therapy, known as CAR-T cell therapy, has proven to be very effective against certain types of blood cance.

It has also been less successful in patients with solid tumors such as brain and bone cance.

Researchers at Stanford University have designed a modified CAR-T cell therapy, called SNIP CAR-T, that can be activated by an oral hepatitis drug already approved for use in humans by the.

After the cells are infused into a patient, the ability to control the activity of the cells with drugs provides a safety mechanism for those who may be less responsive to the genetically modified cel.

"We've created a 'remotely controlled' CAR-T therapy that can be adjusted for each patient," said Crystal Mackall, MD, the Ernest and Amelia Gallo Family Professor of Pediatrics and Medici.

McCall is the senior author of the study, published online April 27 in the journal Ce.

"I was surprised by how much better SNIP CAR-T cells were than traditional CAR-T therapy," Labanieh sa.

Because oral drugs that trigger SNIP CAR-T cell activity are already FDA-approved, the researchers hope to initiate clinical trials in patients with solid tumors within the next 24 mont.

Make immune cells work

CAR-T cells are made from immune cells called T cells, harvested from patients and genetically engineered in the lab to recognize and attack cancers with specific molecules on their surfa.

In 2017, the FDA first approved CAR-T cell therapy for acute lymphoblastic leukemia in children and young adul.

Labanieh wants to develop a CAR-T system that can be easily controlled once the cells are returned to the patie.

Labanieh and colleagues showed that SNIP CAR-T cells were inactive in experimental mice without grazoprev.

"Previous efforts to create drug-regulatable CAR-T cells have produced very finicky or buggy systems," Labanieh sa.

"When the SNIP CAR-T system with the full dose of grazoprevir kicks in, it's fully active," Mackall add.

For solid tumors

When the researchers tested the ability of SNIP CAR-T cells to fight solid cancers in mice, they found that they were more effective than traditional CAR-T therapy -- in many cases, they cured patients with brain cancer called adult canc.

Unexpectedly, they also found that adjusting the dose of grazoprevir made CAR-T cells more discriminating, focusing the killing activity on cancer cells with high levels of the target molecule, without affecting normal cells with low levels of the target molecu.

organizati.

Engineering CAR-T cells to recognize target molecules that also occur on healthy cells would transform their ability to fight solid human tumors, the researchers sa.

"It's a very attractive possibility," McCall sa.

"If we could reduce the activity of SNIP CAR-T cells by varying the dose of grazoprevir, we could personalize treatment for each patient with great precision, preventing toxicity or driving CAR-T cells to kill cancer cells in normal tissu.

We think this is the next generation of cancer therapy that will transform the field of CAR-T cel.

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