After a blood and marrow transplant, doctors expect that a donor’s cells will take over an ill patient’s body and create a new, healthy immune system.
But sometimes those donor cells go too far and attack the patient’s own tissue, resulting in a miserable and potentially deadly complication called graft-versus-host disease (GVHD).
And it’s a big problem. GVHD occurs in about 30 to 40 percent of people receiving blood or marrow from related donors and about 60 to 80 percent of those using an unrelated donor, according to the National Institutes of Health.
But now, by applying basic science research performed at the University of Minnesota, a Masonic Cancer Center physician-scientist has tested a new cellular therapy that may help to prevent this complication. Results from an earlystage clinical trial show promise.
Claudio Brunstein, M.D., Ph.D., gave 23 patients who have blood cancers specialized immune cells called regulatory T-cells in conjunction with their transplant of umbilical cord blood. Regulatory T-cells can suppress other T-cells in the new immune system if they become too aggressive and start attacking the transplant recipient’s body.
“The ultimate goal,” says Brunstein, “is to determine whether the regulatory T-cells can reduce GVHD by better educating the cells from the donor to keep them from attacking the tissues of the patient without reducing the efficacy of the transplant.”
Brunstein says his study not only affirmed the safety of the cells, but GVHD occurrence dropped by about 20 percent in the group receiving the experimental treatment compared with control groups from previous studies who did not receive regulatory T-cells.
GVHD therapies do currently exist, but they are not without risk because they suppress the fledgling immune system, Brunstein says. “There is always a tradeoff—more infection and potential recurrence of the leukemia,” he says.
Brunstein hopes that by essentially using regulatory T-cells to teach the immune system not to attack the patient’s body, GVHD can be prevented in the first place.
In the past, growing enough of these specialized immune cells to transplant has been a challenge.
But thanks to the basic science research done under the direction of the University’s Bruce Blazar, M.D., researchers have developed a technique that coaxes the regulatory T-cells to replicate up to 50-million-fold. Previously, 70-fold replication was the best scientists could do.
Now that Brunstein’s Phase I clinical trial is complete, he hopes to expand it and test the safety of even larger, potentially more helpful doses. Eventually, Brunstein will plan a larger clinical trial that will directly compare patients who receive the cells with those who do not.
“We have seen evidence that they are beneficial,” he says of the regulatory T-cells. “And that gives us the encouragement to push this forward.”