NIH $20 Million Transplant Grant Funds Multiple Pursuits of Advancing Immunosuppression

October 2012

A new $20 million grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health will allow Dr. Chistian Larsen, chair of the Department of Surgery and PI of the program project grant, and a team of Emory physician/researchers to develop better treatments for organ transplant recipients that help avoid both organ rejection and drug toxicity. While the new grant builds on more than 18 years of pioneering immunology research by Emory scientists, such as the development of the immunosuppressant belatacept by Dr. Larsen, Dr. Thomas Pearson, and other investigators at Emory and Bristol-Myers Squibb, it reflects the fact that significant challenges remain for transplant patients over the long term.

"Improvement in these transplant drugs is still a critical need for avoiding acute and late-stage rejection," says Dr. Larsen. "Ultimately, we want to improve overall health while reducing cost through improved outcomes with fewer drugs."

Belatacept was FDA-approved in 2011 for kidney transplant recipients and is currently being tested in experimental clinical trials for kidney transplant, liver transplant, pancreatic islet transplant, and hand transplant. Although belatacept avoids some of the toxicity of earlier transplant drugs, it is associated with higher rates of reversible acute rejection. And because it is a lifelong therapy, it still includes risks associated with a compromised immune system.

"The most important feature of this award is its support for multiple investigators attacking the problems of immunosuppression from different but complementary angles," says Dr. Allan Kirk, vice chair of research of the Department of Surgery. "The team science approach is the best way to get results to our patients."

In addition to Dr. Kirk and Dr. Larsen, the project leaders include transplantation chief Dr. Stuart Knechtle, recent Department of Surgery faculty appointee Dr. Andrew Adams, and Dr. Leslie Kean, director of the Pediatric Bone Marrow Transplant Division of the Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta. The teams will work to develop more effective transplant drugs, adjuvant therapies combined with transplant drugs, and strategies to avoid immunosuppressant drugs altogether.

Specific projects will include development of a new generation of costimulation blockers that will safely and more specifically block immune pathways in combination with a new type of antibody therapy; refinement of chimerism-based strategies, which involve combining costimulation blocking drugs with transplant of the donor's bone marrow along with the organ transplant, ideally leading to tolerance without the need for lifelong drug therapy; and development of methods to overcome immune sensitization in patients who have had previous transplants, pregnancies, or blood transfusions and therefore have an increased risk of rejection.