Reprogrammed donor cells thwart leukemia relapse
In a small study, T cells that were taken from donors and engineered to recognize the Wilms tumor antigen 1 (WT1) and kill leukemia cells were then infused into high-risk and relapsed leukemia patients after stem cell transplantation to promote antileukemic activity and prolong survival.
“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 antileukemic effect, as has been suggested from earlier vaccine trials that induce less potent responses,” explained study coauthor Philip Greenberg, MD, in a statement from Fred Hutchinson Cancer Research Center in Seattle, Washington, where Greenberg heads the immunology program.
In the research, presented in Science Translational Medicine (2013;5:174ra27), Greenberg and colleagues reiterated that relapse remains a leading cause of death after allogeneic hematopoietic cell transplantation (HCT) among patients with high-risk leukemias. (All patients in this study were considered at high risk of death because either they had already relapsed or their leukemia had unfavorable characteristics.) The WT1 protein is overexpressed in leukemias and is partly responsible for why the cells have become leukemic.
Each of the 11 patients in the study received T cells from the same matched donor who had previously contributed the cells for that patient's stem cell transplantation. The best results were achieved when some of the patients received T-cell clones that were exposed to interleukin21 (IL-21) during the programming and growth process (the programmed cells were grown in large numbers before being infused into patients). IL-21 promotes T cell expansion while helping those cells acquire characteristics of central memory T cells.
Of the four patients who received infusions of T cells that targeted WT1 and were generated in the presence of IL-21, one had detectable relapsed disease and went into remission shortly after the T cells were infused. All four survived for more than 30 months without relapse and without developing graft-vs-host disease (GVHD), a major complication of stem cell transplantation. None of these four patients required any additional antileukemic treatment.
Two of the seven patients whose T cells were generated without the presence of IL-21 showed direct evidence of antileukemic activity. One of those two patients had advanced progressive disease and exhibited a temporary response.