Researchers at City of Hope, Stanford University and the University of California, Los Angeles, have developed a method to track genetically engineered, cancerkilling immune cells in the human body.
The tracking method lets researchers monitor the engineered cells’ location and health, and it could be used to determine exactly what the cells are doing at any given time. The system can continue tracking the cells far longer than current methods.
|Michael C. Jensen (Photo by Paula Myers)|
Michael C. Jensen, M.D., associate chair of the Department of Cancer Immunotherapeutics and Tumor Immunology, is a pioneer at arming and programming the immune system’s T cells to hunt down and kill cancer cells. Until recently, however, he could not get a clear picture of what the engineered T cells were doing once they were inside the body.
“This method gives us a much clearer picture than the methods we’ve used up until now,” said Jensen.
Previously, the researchers used a radioactive tag to track the engineered T cells. The tag does not last long, and it gives little or no clue about the cells’ health.
In the current study, Jensen and his colleagues removed 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 naturally seek out and destroy infected or dysfunctional cells in the body.
The researchers then inserted a circle of DNA with two key genes into these T cells: One gave the T cells the ability to home in on the cancer cells; the other helped researchers see the T cells through imaging. That second gene encodes an enzyme found in herpes simplex virus that researchers can use to lock in a radioactive tracer within the engineered T cells. They can detect the tracer using positron emission tomography, or PET.
The herpes enzyme also serves as a safety catch: The researchers can use it to eliminate the T cells after their infusion back into the body if they feel the patient’s safety is threatened.
After modifying the T cells, the researchers reinfused them into the patient’s brain near the tumor site over the course of five weeks. Three days after the last infusion, they gave the patient the imaging agent. As the researchers had hoped, the subsequent PET-CT scan showed that the T cells had homed in on the tumor.
|PET image showing two views of a patient’s brain. T cells appear in light blue as they move in to surround two tumors. (Courtesy of Shahriar Yaghoubi and Sanjiv Gambhir/Stanford)|
Unexpectedly, the T cells also migrated through the patient’s brain to highlight a second, previously unsuspected tumor site.
Although this study did not test the T cells’ ability to kill tumor cells, the imaging results suggested they got to their targets.
“The cells were actually good at finding the tumor,” said Sanjiv Gambhir, M.D., Ph.D., director of Stanford University’s Molecular Imaging Program. Gambhir also pointed out that the same technique could be used to follow other immune cells, or eventually engineered stem cells, throughout the body.
Jensen began engineering T cells to hunt down residual cancer cells — malignant cells that survive initial anticancer therapy — more than 10 years ago. His work, which led to a one-of-akind clinical trial testing these T cells in patients with glioblastoma, also targets lymphoma, neuroblastoma and other cancers.
The imaging study appeared in the January issue of Nature Clinical Practice Oncology.