T-reg Cells Derived from Cord Blood Used in First Clinical Trial for Leukemia

University of Minnesota, September 7, 2007

In order to decrease the risk of immune reactions common in patients undergoing blood and marrow transplantation researchers have taken steps to determine the safety and optimal dose of T regulatory cells (T-regs) at the University of Minnesota.

The groundbreaking clinical trial is being conducted with the hope that it will offer a potential new paradigm for treating autoimmune diseases as well as improve overall survival rates for blood cancer patients.

"Toward our quest of making transplants even safer for adults and children with leukemia, lymphoma, multiple myeloma, and other blood and marrow disorders, we are exploring the possibility of using T-regs to enhance the rate of blood and marrow recovery and reduce the risks of graft-versus-host disease, a complication that affects more than 60 percent of patients," said Claudio Brunstein, M.D., principal investigator of the study.

Normally responsible for regulating the body's immune responses, T-regs are a type of lymphocyte or white blood cell. Helping to ward off life-threatening graft-versus-host-disease (GVHD), donor T-regs may suppress the recipient's immune system so that the healthy donor's blood-forming stem cells and immune cells can grow in transplant cases. When donated cells attack the body of the transplant recipient it is referred to as GVHD. Following transplant, GVHD is responsible for one-third of the deaths.

The risk of GVHD decreases and the chance of blood and marrow recovery increases when T-regs are infused after transplant. This has been proven by researchers using animal models.

"Once we identified that T-regs were highly effective in mouse models, we then spent three years finding ways to make this therapy valuable for transplant patients and potentially useful for patients with autoimmune diseases," said Bruce Blazar, M.D., director of the Center for Translational Medicine at the University.

Since they are easier to expand in culture prior to treatment and occur in higher frequency than what is typically found in most adults, the T-regs in this study are isolated from umbilical cord blood (blood collected from the placenta or afterbirth after the birth of a child). This unique use of umbilical cord blood derived T-regs marks a world first for human clinical trials.

Using patients who are undergoing a double umbilical cord blood transplant for bone marrow failure, leukemia, or other blood cancer; this trial is designed to find the highest possible safe dose of T-regs in these immune suppressed patients. There should be no acute side effects with the T-regs according to researchers who have observed similar results already in animal models.

T-regs will be a powerful therapy to enhance engraftment in transplant patients and prevent GVHD if the data in humans mimics animal models. Conditions such as multiple sclerosis, type I diabetes, and other autoimmune diseases will be treated with the T-regs to test for effectiveness once initial efficacy and safety data is known. The cell may help prevent disease progression if T-regs are transplanted early in the life of the disease hypothesized university researchers.

"This is an exciting time. In the near future, I anticipate being able to combine immune cell populations, like T-regs, that stop immune reactions responsible for autoimmune diseases like diabetes, and immune responses to stem cell infusion given to repair already damaged tissues. This brings great hope not only for adults and children with cancer but many other diseases as well. At the close of this clinical trial, we hope to go right to our first clinical trial with T-regulatory cells in the treatment of newly diagnosed diabetes," said John E. Wagner, M.D., director of the pediatric hematology-oncology and blood and marrow transplantation program at the University of Minnesota.

The Children's Cancer Research Fund, the National Marrow Donor Program, the Leukemia and Lymphoma Society, the National Institute of Allergy and Infectious Diseases, the National Heart Lung and Blood Institute, the National Cancer Institute, and the National Institutes of Health are funding the study.