Tracking T cells in the Brain with Reporter Genes
March 6, 2017 | by Denise Heady
Injecting reengineered CAR-T cells directly into the brain has the potential to be dramatically effective in the treatment of advanced brain tumors.
Early clinical trials at City of Hope proved that CAR-T cells have the power to demolish deadly brain tumors that chemotherapy and radiation could not destroy.
Demonstrating that this technology works in a handful of patients gives us hope that CAR-T therapy will change the way we treat brain tumors,” said Behnam Badie, M.D., chief of neurosurgery at City of Hope.
Although researchers have seen initial success treating brain cancer patients with this type of immunotherapy, questions linger about what exactly happens to these cells once they disperse through the brain.
Did all the T cells find their way to the tumor? Are the T cells causing toxicity?
To help answer these questions, scientists have for the first time demonstrated a way to monitor these cells.
A new study published in Science Translational Medicine, reveals how scientists designed a method to engineer these T cells with something called a “reporter” gene, so they can be tracked and monitored by scientists once they are injected into a patient’s brain.
This technology may help provide an early glimpse of the CAR-T response before conventional imaging is available.
To track the T cells, researchers used a common approach that is similar to Metabolic PET Imaging, a noninvasive imaging technique that detects differences in the metabolism of tissues.
In this method, the reporter gene modifies FHBG — a drug that is similar to an antiviral medication — that can be seen through PET imaging.
To test the method, scientists looked at patients with recurrent glioblastoma enrolled in a City of Hope clinical trial, who received a dosage of CAR-T cells through direct-brain injection.
The PET scans were able to show the T cells’ location and whether or not they made it to the tumor.
While there are still some limitations to this type of imaging technique, it gives researchers a better understanding of T cells and the opportunity to eventually create more powerful ones.
“Tracking cells in the brain is not easy,” said Badie. “This is the first time that this type of imaging modality has been used to look at patients getting cells into the brain and is one demonstration that it could be used in the future for tracking cells,” said Badie.
The study was led by researchers at Stanford University and co-authored by City of Hope’s Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation; Christine Brown, Ph.D., Heritage Provider Network Professor in Immunotherapy; and Behnam Badie, M.D., chief of neurosurgery at City of Hope.