But despite their careful cultivation, the transferred T cells were initially not as effective as the researchers had hoped. Although some benefit was seen, it was short-lived.
The researchers then found that exposing the T cells to interleukin-21 (IL-21), an immune-system molecule, made the cell more resilient and long-lasting without changing what they were trained to recognize, explained study senior author Dr. Philip Greenberg, head of the Program in Immunology at Fred Hutchinson Cancer Research Center and professor of medicine and immunology at the University of Washington in Seattle.
Four leukemia patients were treated with these T cells that were both trained to go after WT1 and were pretreated with IL-21. All four have now been in remission for two or more years since the T-cell therapy was completed, and none have suffered graft-versus-host disease, the researchers reported.
One of these patients was in relapse at the time of the infusion and is now in remission. The other three patients had no detectable disease at the time of the infusion but, given the characteristics of their disease, would have been expected to relapse two to five months after the therapy, Greenberg said.
"T cells produced in this manner not only exhibited greater persistence upon transfer into the patients, but were also far more effective in killing the leukemia cells," said Wiest. "The ramped-up T cells not only fought off the leukemia but did so over a sustained period of time."
The researchers believe the protocol could not only treat different types of leukemia but perhaps also other cancers in general.
"Because WT1 is not only expressed in leukemia but broadly across tumors, the goal is to use [these types of cells] to treat other cancers," said Chapuis, who is a research associate at Fred Hutchinson Cancer Research Center and acting instructor at the University of Washington Medical Center in Seattle.
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