Grant: Team Grant: Preparation to Trial: Inflammation for Chronic Conditions

Bone marrow and organ transplantation is often the only cure for a number of life threatening diseases. Unfortunately, chronic rejection is a possible outcome for 10-70% of transplants. Patients that receive a bone marrow transplant can develop life-long rejection of many organs in their body by the immune system that is part of the transplanted bone marrow. This chronic immune rejection by the transplanted bone marrow is called chronic graft-versus-host-disease (cGvHD). In our work with patients, who have received bone marrow transplants, we found that cGvHD is far less likely to develop in patients that have a higher number of a specific type of immune cells called a regulatory natural killer cells (NKregs). Our goal is to determine whether NKregs can be isolated from either healthy bone marrow transplant donors or kidney transplant recipients and grown in a lab to increase their numbers, and then used as a therapy to prevent transplant rejection. In this research, we will develop protocols to isolate and grow human NKregs in the lab, and test whether administering NKregs, alone or in combination with a new engineered drug that can cause them to expand in the blood, can prevent transplant rejection. If successful, we will have developed a new understanding of how NKregs extend the life of transplanted tissue and improve the long term quality of life and learn the best way to expand NKregs for patient use, leaving us well-poised for clinical trials.