Ways to prevent deadly complications were developing in a study on mice

Sep 28, 2012 13:49 GMT  ·  By
New study on lab mice shows how to prevent stem cells transplants from killing recipients, and make the T-cells start killing leukemia cells instead
   New study on lab mice shows how to prevent stem cells transplants from killing recipients, and make the T-cells start killing leukemia cells instead

Researchers at the Washington University in St. Louis (WUSL) say that data collected during a new study conducted on unsuspecting lab mice may soon help doctors perform stem cells transplants that have fewer deadly complications and negative side-effects than they do now.

The investigation was conducted using mouse models of leukemia, a type of blood cancer that can only be addressed effectively with stem cells, after chemotherapy and radiotherapy fail. When the first line of treatment fails, transplants become the only possible solution.

But these transplants are not without risk. Around half of the people who receive them develop what is known as graft-versus-host disease, which means that their bodies reject the newly-inserted cells.

Immune system cells from the donor begin to attack the patient’s own body, causing irreparable damage, and eventually leading to death. The skin, liver and gut are the first to come under attack.

In the new study, the team was able develop a way of keeping these keen immune cells away from transplant recipients' organs, and redirecting them towards killing cancer cells – which was their intended purpose to begin with.

“This is the first example of reducing graft-versus-host disease not by killing the T-cells, but simply by altering how they circulate and traffic,” WUSL researcher John F. DiPersio, MD, PhD, explains.

“Donor T-cells do good things in terms of eliminating the recipient’s leukemia, but they can also attack normal tissues leading to death in a number of patients. The goal is to minimize graft-versus-host disease, while maintaining the therapeutic graft-versus-leukemia effect,” he goes on to say.

The investigator holds an appointment as the Virginia E. and Sam J. Golman professor of medicine at the university. Details of the experiments appear in a recent online issue of the scientific journal Blood.

The key to solving this problem was targeting the interferon gamma receptor protein on the surface of donor T-cells. Eliminating, or even blocking, this molecule prevented the immune cells from migrating to the skin, liver or gut, but still left them perfectly capable to kill blood cancer cells.

“The fact that blocking the interferon gamma receptor can redirect donor T-cells away from the gastrointestinal tract, at least in mice, is very exciting because graft-versus-host disease in the gut results in most of the deaths after stem cell transplant,” DiPersio concludes.