If the immune system is an army, then T-cells are soldiers on the front lines, attacking invading viruses and other agents of disease. But not every soldier is the same; some units have skills and equipment that makes them the best at certain tasks.
Similar to units in an army, T-cells can be divided into groups by their age and the kind of receptor they use to attack other cells. And a new study published today by scientists at the Fred Hutch Cancer Research Center, combined with new technology that can track the cells, has discovered that some rare T-cells are particularly effective at fighting cancer.
The discovery and the new tech will be important for scientists developing CAR-T immunotherapies, treatments that reprogram a person’s T-cells to fight cancer.
The tech was developed by Seattle-based Adaptive Biotechnologies, and it assigns a “barcode” to each T-cell based on the kind of T-cell receptor (TCR) it has. This allows researchers to track different kinds of T-cells in the lab and in patients’ bodies.
In the study, researchers prepared immunotherapy treatments for ten melanoma patients by reprogramming a sample of their T-cells to find and destroy cancer cells. Those reprogrammed cells were then multiplied in a lab and infused back into the patient.
Unlike previous immunotherapy studies, the researchers were then able to see which T-cell types were most effective at fighting the patients’ cancer. Two of the patients went into remission, and by studying the makeup of their T-cells researchers were able to identify a set of cells that appear to be particulalry effective against cancer.
Fred Hutch researcher Dr. Aude Chapuis, who led the study, told GeekWire in an email that the more effective cells likely had two traits that set them apart.
First, they all appear to be young T-cells, which means they “have a huge potential to proliferate and survive in the face of large quantities of antigen,” she said. In other words, the cells will continue to multiply and resist being worn out even after repeatedly attacking cancer cells.
Second, Chapuis said they may have a TCR that is particularly good at finding cancer cells. That means even after most of the cancer cells have been destroyed, they can “still seek-out [sic] the tumor left behind and get rid of it,” she said.
The bad news is that these young, effective cells are very rare: of the almost 5,000 types of T-cells the study looked at, only two fit into this category.
The good news is that by growing cells selectively, researchers are able to increase the number of highly effective cells, possibly making immunotherapy treatments more effective as well.
Chapuis said she and her team are currently working on this prospect in a clinical trial. Instead of infusing patients with a random mix of T-cells, they will specifically use two types of young T-cells. Chapuis said the goal is to see which of the two groups is most effective against patient’s cancer.
She also said she is doing more in-depth research on the effective cells they found in the study to confirm their hypothesis that they have highly effective TCRs.
All of this research is underpinned by the “barcode” tech developed by Adaptive, known in the industry as “high-throughput receptor sequencing” technology.
Chapuis said the tech is helping her and other researchers understand more about T-cell receptors, and will be instrumental to developing more and more effective treatments.
“Overall we are using the barcoding to go to the next level: select high affinity TCRs from the general population to then rapidly screen and select the most high-affinity TCR to use for gene-therapy,” she said.
The study and the barcode tech also helps the field move toward answering one of the biggest questions in immunotherapy: why do some patients react to treatment, while others do not?
While we are still a long way from knowing the answer to that question, Chapuis’ research is helping to learn more about the cells that make immunotherapy work and the characteristics that set them apart.
