The National Institute of Allergy and Infectious Diseases has awarded Emory transplant researchers $12.6 million over five years to investigate improved post-transplant drug regimens for organ transplant recipients.

The project team is led by professor of surgery Christian Larsen, MD, DPhil and includes Mandy Ford, PhD and Andrew Adams, MD, PhD at Emory, and Leslie Kean, MD, PhD at Seattle Children’s Hospital and the University of Washington. The project continues Larsen’s work, undertaken with Thomas Pearson, MD, DPhil at Emory, on costimulation blockers, drugs to prevent immune rejection of transplanted organs.

Costimulation blockers interfere with T cell function, halting immune rejection of a transplanted organ, while avoiding damage to the kidney and cardiovascular system observed with transplant drugs such as cyclosporine and tacrolimus, known as calcineurin inhibitors.

Together with Bristol-Myers Squibb, Larsen and Pearson developed a costimulation blocker called belatacept. It was shown in a multi-center clinical trial to improve graft survival and mortality rates in kidney transplant patients, in comparison with calcineurin inhibitors, the standard of care in the past. However, in these studies, acute rejection rates were higher with belatacept than with calcineurin inhibitors.

“Our research is aimed at extending the benefits of costimulation blocker-based regimens to a larger group of transplant patients, and helping them to have longer, healthier lives,” Larsen says.

The team’s recent research has identified biomarkers on immune cells that may predict the likelihood of costimulation blocker-resistant graft rejection. The current project will examine these biomarkers’ predictive value in non-human primate models of organ transplant, in cooperation with Yerkes National Primate Research Center. The team will also investigate pathways for targeting immune cells that are resistant to costimulation blockers, as well as cellular therapies and strategies for preserving protective immunity against viruses in organ transplant recipients.