A new technique will allow doctors to identify which T-cells in the soup of immune cells that are taken from a patient are most likely to combat a tumor.
The technique involves using T-cell receptors to track the cells themselves once the T-cells are back in the patient’s body.
Most T-cells don’t combat a tumor. That explains why treatments with mixes of cells whose propensities toward a tumor are unknown often fail to work, researchers said.
The study, “Tracking the fate and origin of clinically relevant adoptively transferred CD8+ T cells in vivo,” was published in the journal Science Immunology.
“We found that the cells in each patient’s immune system that will ultimately have a clinical effect are incredibly rare,” Dr. Aude Chapuis, the study’s lead author, said in a press release. She is a member of the Clinical Research Division at Fred Hutchinson Cancer Research Center in Seattle.
“Knowing what we’ve found, we can now refine the selection of the cells that we will ultimately use for adoptive T-cell transfer, so that the cells persist and keep the tumors at bay longer in our patients,” Chapuis said.
Cell-based cancer immunotherapy has been hampered by lack of knowledge about the specific cells involved in the tumor-fighting process. The body contains thousands of types of T-cells, each with a distinct capacity to combat cancer.
When researchers gather immune cells from a patient, they first alter them to be more efficient in fighting a cancer. The next step is to grow the tweaked cells in a lab dish. Then researchers inject them back into a patient.
The process can change the appearance and behavior of cells, making it even more complicated to keep track of those targeting a tumor.
A Hutchinson cancer center spin-off, Adaptive Biotechnologies, is doing work that will help doctors identify and track cells with the most desirable cancer-fighting properties.
Adaptive Biotechnologies’ research focuses on the fact that a T-cell’s identity stems largely from its surface receptors, key tools the cells use to fight infections or cancer.
The new method that researchers are using to identify the T-cells most likely to combat cancer is called high-throughput T-cell receptor sequencing. It essentially involves giving each T-cell a bar code that can be used to track the cell once it is back in the patient, the researchers explained.
“High throughput T-cell receptor sequencing allows us to distinguish the cells and figure out where they came from, which ones grow in culture and which ones persist after being transferred to the patient,” said Chapuis, who is also an assistant professor at the University of Washington School of Medicine. “We can finally track in detail what’s going on when doing adoptive T-cell transfers,” she said.
Using the new method, the research team examined the T-cells that were in the mix given to 10 patients with metastatic malignant melanoma. Then they correlated the different cells’ presence with the treatment response.
Only two of the 10 patients went into complete remission, but they offered clues about what a cancer-fighting T-cell looks like. It turned out that the cell type that was most common in the two patients was extremely rare in the mix of immune cells that was taken from them.
Researchers also discovered that younger T-cells had a better ability to fight tumors than older ones.