HOUSTON – (April 13, 2012) – A researcher at The University of Texas Health Science Center at Houston (UTHealth) is studying a novel cell therapy that could help avoid autoimmune problems after stem cell transplantation, as well as potentially treat other autoimmune diseases.
The preclinical study, funded with a $1.9 million grant from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI), is being conducted in collaboration with the NIH and The University of Texas MD Anderson Cancer Center.
The therapy centers on regulatory T cells, which are central to the control of autoimmunity in the body. Dat Tran, M.D., assistant professor in the Pediatric Research Center at the UTHealth Medical School, said the therapy could help prevent graft-versus-host disease (GVHD), an autoimmune disorder that occurs in up to 80 percent of cancer patients receiving bone marrow stem cell transplants. It could also potentially treat other autoimmune diseases such as type 1 diabetes.
“Leukemia and lymphoma are blood cell cancers, immune system cancers. You have to wipe out the whole immune system and then give the person a new system through a stem cell transplant,” said Tran, who holds a dual appointment in the UTHealth Department of Pediatrics Division of Allergy, Immunology and Rheumatology. “But the immune system is designed to detect foreign particles and attack them. Depending on how close the match is, you can have a reaction between the graft donor and the host patient that results in an autoimmunity problem.”
According to the National Institutes of Health, GVHD occurs in 30 to 40 percent of recipients using related donors and 60 to 80 percent in recipients using unrelated donors. Acute symptoms include abdominal pain, diarrhea, fever, jaundice, skin rash, vomiting and weight loss. Chronic symptoms include dry eyes and mouth, hair loss, hepatitis, lung and digestive tract disorders and skin thickening. Some cases can lead to death.
The most effective treatments are high-dose corticosteroids, which often have severe side effects. “That’s not good enough,” Tran said.
While working at the National Institutes of Health as an allergy and immunology fellow, Tran began to research ways to enhance the regulatory T cells in the body.
“Regulatory T cells are extremely important because if you don’t have them, your body will develop autoimmunity and attack itself,” he said. “We think perhaps the regulatory T cells don’t develop fast enough in stem cell transplants. So I thought, ‘Why don’t we put the regulatory T cells in the body before the transplant to enhance transplantation and avoid autoimmunity?’ ”
The challenge, he said, was finding a way to grow the T cells in large enough quantities and separate out the best ones to achieve a more potent population. He found a marker they could use to isolate the good regulatory T cells and published a proof-of-theory paper in the May 2009 issue of the American Hematology Society journal Blood.
“We’re now testing the cells in mice to see if they are stable and potent and that they will work,” he said. “In the next five years, in collaboration with MD Anderson, we hope we can prevent GVHD.”
Co-investigators for the study include Daniel Douek, M.D., Ph.D., chief, Human Immunology Section, NIH Vaccine Research Center; Amin Alousi, M.D., assistant professor of medicine, Department of Stem Cell Transplantation at MD Anderson; and Laurence Cooper, M.D., Ph.D., professor of pediatrics and section chief, Cell Therapy at MD Anderson.
Deborah Mann Lake
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