Immune Tolerance in Transplantation
Each year, nearly 29,000 organ transplants are performed in the United States. For all of these people, anti-rejection therapies known as "immunosuppressive drugs" are a lifeline that prevents their body from rejecting the transplant. A number of immunosuppressive medications are available that have proven quite successful at preventing rejection over the short term. However, these drugs work by suppressing all of the immune system - even the parts that protect from real threats. This means that people taking immunosuppressive drugs are at risk of developing serious infections, and sometimes even cancer. Additionally, immunosuppressive drugs only work for as long as a patient is taking them. Once a patient stops, they are at risk of rejecting the transplant.
The Immune Tolerance Network (ITN) is working to find new, more specific immune tolerance therapies. These therapies are medications and techniques that are designed to reprogram the immune system so that it learns to tolerate the presence of a transplanted organ or tissue, but leaves the disease-fighting parts to continue their good work. These therapies would ideally be short-term, meaning that they don't need to be taken every day for life, but would still have a lasting effect against transplant rejection.
Research Focus - Transplantation
The ITN conducts solid organ transplant studies with two complementary goals. The primary goal of our interventional studies is to achieve the complete and planned withdrawal of all immunosuppression while maintaining the healthy function of the graft organ. The ITN is also looking for biomarkers of tolerance that would be useful in predicting when transplant patients can be weaned from immune suppressive drugs. By continuing registry studies of operationally tolerant kidney transplant patients, the ITN aims to validate previously identified biomarker signatures as well as better understand the mechanisms of tolerance. In addition, immunosuppression-tapering studies in liver transplant recipients have enabled drug-free allograft survival among a number of patients and the ITN will build on these studies to identify biomarkers of tolerance in similar cohorts of patients.
The ITN also conducts novel interventional studies to actively guide the immune system towards acceptance and tolerance of a transplanted organ. Previous ITN trials demonstrated that induction of transient chimerism (the simultaneous presence of donor and recipient immune systems) via combined bone marrow and kidney transplant can achieve operational tolerance in some individuals. Building on this success, the ITN is pursuing new approaches that combine therapeutic cell transfers with solid organ transplantation to create an immunological environment that facilitates tolerance.