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Take a peek into the killer world of T cells 

 



by Darrin S. Joy and Alicia Di Rado
 

Remember playing hide-and-seek? Well, imagine how the game would change if you had X-ray vision.

Now a team of cancer researchers just got that advantage.

PET image showing different views of a patient’s brainPET image showing different views of a patient’s brain as T cells (light blue) move in to surround two tumors. (Photo courtesy of Shahriar Yaghoubi and Sanjiv Gambhir/Stanford)
Scientists at City of Hope rewired special immune cells to go after and kill cancer, and together with their partners at Stanford University and the University of California, Los Angeles, developed a way to watch the cells in action — even though the cells are deep inside the brain.

It began in the lab of Michael C. Jensen, M.D. He’s known for an experimental, innovative strategy to attack cancer using the immune system: He programs T cells to hunt down cancer cells. Until recently, though, he couldn’t get a clear picture of what these engineered T cells were doing after they were injected into the body.

“This method gives us a much clearer picture than the methods we’ve used up until now,” said Jensen, associate chair of City of Hope’s Department of Cancer Immunotherapeutics and Tumor Immunology.

In the study, Jensen and his colleagues gathered cytotoxic, or ‘killer,’ T cells from the blood of a patient with glioblastoma, the most common and deadly form of brain cancer.

Killer T cells are the kind that normally defend the body by destroying infected or broken cells.

First, the researchers engineered the patient’s T cells to home in on brain cancer cells; then they added a gene that let the researchers track the T cells wherever they scurried in the body — almost as if they had X-ray vision.

Here’s how it works: The gene helps the T cells grab and hold onto a type of radioactive “flag.” After the researchers injected the T cells into the patient, they gave him a special solution with the radioactive flag, which the engineered T cells snatched up. Then the researchers scanned the patient through high-tech imaging, hoping that those radioactive flags would show up on the scans, wherever the T cells were.

And just as they thought, hotspots on the scan showed that the T cells had found the tumor. Unexpectedly, the T cells also migrated through the patient’s brain to a second tumor no one knew about.

Although this study didn’t test the T cells’ ability to kill tumor cells, the imaging results suggested they got to their targets. The researchers will refine their techniques further in future studies.

The study appeared in the January issue of Nature Clinical Practice Oncology. It was supported through funding from the National Institutes of Health and the Doris Duke Foundation.

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