Fred Hutch scientists use novel ‘barcode’ system to find effective cancer-killing T cells

Chimeric antigen receptor T cells, or CAR-T treatments, are all the rage in the oncology community now, as Novartis and Kite Pharma gear up to seek FDA approval for the new technology in treating blood cancers. Those treatments are made by taking immune-boosting T cells from the blood of individual patients, engineering them to recognize their particular cancers, and then reinfusing them.

One big challenge of using T cells to treat cancer is that each infusion contains thousands of different varieties of the cells, some of which are much more effective at killing cancer than others are. And their cancer-killing prowess could very well change when they are primed to duplicate in the lab.

So scientists at the Fred Hutchinson Cancer Research Center in Seattle have come up with a new way to find the cells that are most likely to lead the attack against tumors. They did it by genetically sequencing T cells taken from 10 patients with melanoma, in essence giving each individual cell its own “barcode,” according to a release from Fred Hutch. Then they watched the cells after they were infused back into the patients.

Two of the patients went into remission. The Fred Hutch team was able to determine that the specific T cells that led the attack on those two patients’ tumors had been “incredibly rare” in their immune systems originally, said Aude Chapuis, a member of the Clinical Research Division at Fred Hutch, in the release. What’s more, the most powerful T cells were younger than the other T cells in the mix. That makes sense: Younger cells are better able to multiply and survive, making them well suited to long-term tumor control. Chapuis was the lead author of the paper, which was published in Science Immunology.

The technology used to sequence the T cells was originally developed at Fred Hutch and spun out into the company Adaptive Biotechnologies in 2009. Adaptive has since raised over $400 million in six funding rounds from a large list of investors that includes Celgene, Matrix Capital Management and DNA sequencing giant Illumina.

Improving upon T-cell treatments is a priority in the oncology community. Earlier this month, researchers from the Mayo Clinic and the University of Washington described a new culture method that improves the ability of T cells to recognize cancer cells and target them for destruction. They used their technique to raise “T cell armies” that recognize three proteins abundant in many cancer types.

The discoveries by Chapuis and her team could prove useful to T-cell researchers going forward, as they search for ways to improve response rates and make the technology applicable to different tumor types. "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," she said.