But they also observed significant variation in how sensitive the modified T-cell receptors were to WT1. That sparked a hunt for a T-cell receptor with an exceptionally strong affinity for the protein. The researchers screened cells from many healthy donors before finding one receptor that was especially "sticky" for WT1. Using the sticky receptor as a blueprint, the team could insert genetic instructions for it into other T cells, enabling them to make this anti-WT1 receptor.

Billions of these engineered T cells were given to each of the 12 AML patients on the trial. More than three years later, the researchers could still detect T cells in these patients that expressed the genetically modified receptor — suggesting this type of treatment could provide long-lasting protection against the return of cancer, Chapuis said.

‘Our 2.0 will be better’

The study also offers a proof-of-principle that scientists could expand the number of targets for engineered T-cell therapies, Chapuis said. The approach of creating an optimal T-cell receptor could extend cell therapy to many more types of cancers. “Successfully going after WT1 opens the door to more targets for immunotherapy,” Chapuis said.

The researchers said that the particular T-cell receptor technology used in this trial won’t be developed further for patient use. But as they’ve been doing for years, Chapuis, Greenberg and Fred Hutch colleagues will continue to refine and improve their approach based on what they’ve learned in the hopes of bringing immunotherapy to more patients. They’re already working in the lab on the next iterations, which aim to make these treatments more effective and longer-lasting.

“We’ve learned a lot through this trial,” Chapuis said. “Our 2.0 will be better as we go from bench to bedside and back again.”

This research was supported by grants from the National Institutes of Health as well as funding from the Damon Runyon Cancer Research Foundation, the Guillot Family (in honor of Zach), Fred Hutch’s Immunotherapy Integrated Research Center, and Juno Therapeutics, a Celgene company.

Competing Interests: Drs. Aude Chapuis and Phil Greenberg have received research funding from Juno Therapeutics. Greenberg consults for and previously had an ownership interest in Juno.

Note: Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.