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Infusion of stem cells and specially generated T-cells from same donor improves leukemia survival
Date:2/27/2013

SEATTLE In a significant advance for harnessing the immune system to treat leukemias, researchers at Fred Hutchinson Cancer Research Center for the first time have successfully infused large numbers of donor T-cells specific for a key anti-leukemic antigen to prolong survival in high-risk and relapsed leukemia patients after stem cell transplantation. Both the stem cells for transplant and the T-cells came from the same matched donors.

Reporting results of a pilot clinical trial in the Feb. 27 issue of the journal Science Translational Medicine, researchers describe the use of T-cells that were taken from a donor, programmed in the lab to recognize the Wilm's Tumor Antigen 1 (WT1) and kill leukemia cells, grown in large numbers, and then infused into patients to promote anti-leukemic activity. The WT1 protein is overexpressed in leukemias and is in part responsible for why the cells have become leukemic.

The best results were achieved when some of the patients received T-cell clones that were exposed to interleukin 21 (IL-21) during the programming and growth process, based on the hypothesis that such exposure would create cells that could survive longer and produce greater anti-leukemic activity after transfer. IL-21 promotes T-cell expansion while helping those cells acquire characteristics of central memory T-cells.

"This is the first time patients have received an infusion of WT1 specific T-cells, and thus also the first demonstration that such cells can provide a therapeutic anti-leukemic effect, as has been suggested from earlier vaccine trials that induce less potent responses," said Philip Greenberg, M.D., corresponding author and head of the Immunology Program at Fred Hutch.

"Ours is also the first report to show that greatly improved T-cell in-vivo persistence can be achieved after transfer by modifying the way cells are generated in tissue culture for therapy with inclusion of the cytokine IL-21," said Aude Chapuis, M.D.
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Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
Source:Eurekalert

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