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.

Measuring Allospecific Impact of Belatacept/Carfilzomib Desensitization (ADAPT)

Principal Investigator:

Stuart Knechtle, MD | Duke University Hospital

The goal of the ADAPT study is to study whether using two drugs, carfilzomib and belatacept, together can lower the number of plasma cells in “highly sensitized” people on the kidney transplant waiting list.

Category: 

Transplantation

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Specific Category: 

Kidney Transplantation

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Status: 

Active

Daratumumab plus belatacept desensitization trial (ATTAIN)

Principal Investigator:

Flavio G. Vincenti, MD | University of California, San Francisco Medical Center

The goal of ATTAIN is to study whether using two drugs, daratumumab and belatacept, together can lower the number of plasma cells in “highly sensitized” people on the kidney transplant waiting list.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

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Status: 

Active

Tolerance by Engaging Antigen During Cellular Homeostasis (TEACH)

Principal Investigator:

Allan Kirk, MD, PhD | Duke University School of Medicine

TEACH is a clinical trial investigating whether cells from the kidney donor's bone marrow, called mesenchymal stromal cells (MSCs) will allow kidney transplant recipients to stop immunosuppressive medications.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

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Status: 

Active

Liver Transplantation with Tregs at MGH and UCSF (LITTMUS)

Principal Investigator:

James Markman, MD, PhD | Massachusetts General Hospital | Boston, MA

Sandy Feng, MD, PhD | University of California San Francisco | San Francisco, CA

LITTMUS is a clinical research study testing a new approach to achieve transplant tolerance using the liver transplant recipient’s own T regulatory cells (Tregs).

Category: 

Transplantation

|

Specific Category: 

Liver Transplantation

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Status: 

Active

Evaluation of Donor Specific Immune Senescence and Exhaustion as Biomarkers of Tolerance Post Liver Transplantation (OPTIMAL)

Principal Investigator:

James Markmann, MD, PhD | Massachusettes General Hospital | Boston, MA

OPTIMAL is a clinical trial that will be investigating immunosuppression withdrawal in liver transplant recipients.

Category: 

Transplantation

|

Specific Category: 

Liver Transplantation

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Status: 

Active

Pilot Study Using Donor Stem Cells and Campath-1H to Induce Renal Transplant Tolerance

Principal Investigator:

George W. Burke | University of Miami | Miami, FL

Alemtuzumab is a man-made antibody used to treat certain blood disorders. This study will evaluate treatment of kidney transplant recipients with alemtuzumab and other immune system suppressing medications with or without infusions of bone marrow stem cells from the kidney donor. The purpose of this study is to find out which strategy is more effective in preventing organ rejection and maintaining patient health.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

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Status: 

Completed

Belatacept to Prevent Organ Rejection in Kidney Transplant Patients

Principal Investigator:

Flavio Vincenti | University of California | San Francisco, CA

Christian Larsen, MD | Emory University | Atlanta, GA

Belatacept is an experimental medication shown in clinical trials to have immune system suppression properties in people who have had kidney transplants. This study will determine whether a combination of anti-rejection drugs, including belatacept, can prevent the rejection of a first-time, non-HLA identical kidney transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

|

Status: 

Completed

Campath-1H/Tacrolimus/Sirolimus Withdrawal in Renal Transplantation

Principal Investigator:

Stuart Knechtle | University of Wisconsin | Madison, WI

The purpose of this study is to test the safety and effectiveness of using alemtuzumab in combination with two other drugs, sirolimus and tacrolimus, to prevent organ rejection after kidney transplantation. This study will also test whether this combination of medications will allow patients to eventually stop taking antirejection medications entirely.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

|

Status: 

Completed

Mixed Chimerism and Renal Allograft with Non-Myeloablative Conditioning in Patients with ESRD Due to Multiple Myeloma

Principal Investigator:

Megan Sykes | Massachusetts General Hospital | Boston, MA

The purpose of this study is to determine whether a combined bone marrow and kidney transplant will be effective in treating stage II or greater multiple myeloma and associated kidney failure. This study will determine whether transplant rejection and the need for immunosuppressive drugs are decreased with this combined transplant approach.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

|

Status: 

Completed

Mixed Chimerism I: Renal Allograft Tolerance Through Mixed Chimerism

Principal Investigator:

David H. Sachs | Massachusetts General Hospital | Boston, MA

A. Benedict Cosimi | Massachusetts General Hospital | Boston, MA

This study examines the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.

Category: 

Transplantation

|

Specific Category: 

Kidney Transplantation

|

Status: 

Completed

Multicenter Trial of Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol

Principal Investigator:

James Shapiro | University of Alberta | Edmonton, Alberta | Canada

This was a multicenter clinical trial of the Edmonton protocol for islet transplantation.

Category: 

Transplantation

|

Specific Category: 

Islet Transplantation

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Status: 

Completed

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