Discovery and Translational Research at the Emory Transplant Center

Researchers at the Emory Transplant Center (ETC) strive to integrate clinical and academic advances, offering extraordinary accomplishments in the field of transplantation. Research conducted by faculty of Emory's Division of Transplantation is done under the auspices of the Transplant Immunology Laboratory, and include programs specific to kidney, pancreas, heart, liver, lung, bone marrow, and composite tissue transplantation.

Many of the lab's efforts are multi-disciplinary and include the following notable projects:

Belatacept Development

In June 2011, the FDA approved belatacept in the form of the drug Nulojix for kidney transplant recipients, which is the first time a new class of drug has been approved for transplant since the 1990s. Emory surgeon-scientists played a leading role in discovering belatacept and driving its development.

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Emory transplant surgeons-scientists, Christian P. Larsen, MD, DPhil, Dean of the Emory University School of Medicine and Joseph B. Whitehead Professor, Department of Surgery at Emory University School of Medicine, and Thomas C. Pearson, MD, DPhil, Executive Director of the Emory Transplant Center, Medical Director, Kidney Transplantation, and Livingston Professor, Department of Surgery at Emory University School of Medicine, began developing belatacept in collaboration with other investigators at Emory University and researchers at Bristol Myers Squibb in the 1990s. Belatacept is a costimulation blocker that inhibits one of the two signal T cells required to trigger an immune response. At the Sixth Annual Joint Meeting of the American Society of Transplant Surgeons in 2005, Dr. Larsen presented the results of a randomized, Phase II study in kidney transplant patients comparing belatacept with the traditional cyclosporine immunosuppressant calcineurin inhibitor, which has known toxicities with long-term use. Dr. Larsen and his colleagues concluded that the drug showed promise as an alternative to calcineurin inhibitors as a primary maintenance therapy.

Dr. Larsen, Dr. Pearson, and their colleagues published the data from two international Phase III clinical trials of belatacept in the March 2010 issue of American Journal of Transplantation, concluding that it can prevent graft rejection in kidney transplant recipients while better preserving kidney function, can maintain lower blood pressure and cholesterol when compared to standard immunosuppressive drugs, and can be given once every few weeks compared with the twice daily dosing regimens necessary for standard immunosuppressive drugs. More patients experienced acute rejection under belatacept, though in most cases the rejection was successfully treated with drugs and did not lead to graft failure.

In March 2010, an outside committee of U.S. regulatory advisers recommended that the FDA approve belatacept for the prevention of kidney transplant rejection. In June 2011, the FDA approved belatacept in the form of the drug Nulojix for kidney transplant recipients, which is the first time a new class of drug has been approved for transplant since the 1990s. Belatacept is now being tested in experimental clinical trials for liver transplant and pancreatic islet transplant.

Clinical Trials in Organ Transplantation Project

As a part of the Clinical Trials in Organ Transplantation (CTOT) project, the Emory Transplant Immunology Lab is one of a handful of centers that is setting the national agenda for new developments in organ transplantation and drug therapy.

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The Clinical Trials in Organ Transplantation (CTOT) project is an investigative consortium for conducting clinical and associated mechanistic studies in transplantation sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), with co-funding from the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). As part of the CTOT, the Emory Transplant Immunology Lab is one of a handful of centers that is setting the national agenda for new developments in organ transplantation and drug therapy.

In 2008, Alan Kirk, MD, PhD, Professor and Scientific Director of Emory Transplant Center, received a five-year grant totaling approximately $6 million from the pediatric arm of the program, known as Clinical Trials in Organ Transplantation in Children (CTOT-C). The study has two components: cataloging and defining how pediatric kidney transplant patients' T cell repertoires evolve as they get older, and developing a simple blood or urine test to replace the painful biopsy that determines whether kidney transplant recipients are undergoing rejection.

The CTOT awarded Dr. Christian P. Larsen, MD, DPhil, director of the Emory Transplant Center, Joseph B. Whitehead Professor and chair, Department of Surgery at Emory University School of Medicine, and Dr. Kirk a five-year grant in 2009 to lead a multi-center study of belatacept-based immunosuppressant therapy regimens. Emory's partners in the program are the University of Alabama Birmingham, University of California San Francisco, and Stanford University.

Juvenile Diabetes Research Foundation (JDRF) Center for Islet Transplantation

In 2003, the Emory Transplant Center performed the first successful islet transplant in Georgia for a patient with Type 1 diabetes (as of August 2010, Emory transplant surgeons have performed 22 successful islet transplant procedures on 15 patients). The Center continues to receive funding from the JDRF to continue its research.

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The Juvenile Diabetes Research Foundation (JDRF) for Islet Transplantation at Emory was launched in 2002 with a $4.1 million grant from the JDRF to fund studies to reduce the requirements for immunosuppressive drugs in islet transplants while increasing the supply of donated islets. In 2003, Christian P. Larsen, MD, DPhil, then director of the Emory Transplant Center (ETC), now dean of the Emory University School of Medicine, and Thomas C. Pearson, MD, DPhil, current executive director of the ETC and director of its kidney transplant program, performed the first successful islet transplant in Georgia for a patient with Type 1 diabetes.

From March 2003 through October 2005 eight recipients underwent islet transplants at Emory University for the ETC’s initial human clinical trial, the Emory-Edmonton Protocol. The ETC then received additional five-year funding from the JDRF of nearly $8.5 million in 2006. The second trial under the JDRF center grant, “Development of immunosuppressive regimens to facilitate single donor islet transplantation using efalizumab,” was launched that year, and five subjects received single donor islet transplants between December 2006 and April 2009.

In March 2007, the JDRF awarded the ETC a $2.5 million grant over three years to develop pig islets as an alternative to human donor islets. The grant funded development of a non-human primate model at Yerkes National Primate Research Center. This effort involved distinguished Emory diabetes researcher Dr. Collin Weber, co-principal investigator of the JDRF Center, and other JDRF Center and Emory Transplant Immunology Lab researchers.

The Emory islet transplant program continues to offer autologous islet transplantation after total pancreatectomy for select patients with refractory chronic pancreatitis. While this program is not directly under the auspices of the JDRF Award, the islet cell isolations and subsequent infusions assist in maintaining the proficiency of the islet transplant team and offer a treatment option to patients who would otherwise be faced with certain lifelong diabetes. Since 2004, ETC surgeons have performed 15 autologous islet transplant procedures. As of 2013, the center is following 30 patients who have received islet transplants.

Microsurgery and Composite Tissue Transplantation

In March 2011, Emory successfully performed Georgia’s, and the Southeast at large, first complete hand transplant. This puts Emory among only four centers to have successfully performed this procedure in the U.S.

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Linda Cendales, MD, Assistant Professor of Surgery at Emory University School of Medicine, is the director of the Vascularized Composite Transplantation and Microsurgery Laboratory of the Emory Transplant Center. Composite transplantation is the re-transplantation of multiple tissues such as skin, muscle, bone, nerve and tendon as a functional unit, such as a limb. Dr. Cendales helped organize the team that performed the first hand transplant in the United States in 1999 in Louisville, KY.

As an international leader in this field, Dr. Cendales provided the consensus update of the Banff classification system on composite allograft histopathology at the annual meeting of the International Hand and Composite Tissue Allotransplantation Society in October 2009. The Banff system was developed by Dr. Cendales and her colleagues at the Ninth Banff Conference on Allograph Pathology in 2007 to categorize the severity of rejection after transplantation of different types of vascularized tissue. Also in fall 2009, the lab and Dr. Cendales as PI received an award of $4 million from the U.S. Department of Defense for the development of a vascularized composite allotransplantation program and began conducting the first clinical trial of CTA in hand transplantation. In March 2011 Dr. Cendales directed the first hand transplant at Emory and in the Southeast at large.

Protective Immunity Project

The Emory Transplant Center received a bio-defense contract to study protective immunity in transplant recipients. The study will help to develop new strategies for vaccination that can better protect organ transplant recipients and other immune-suppressed patients from infectious disease threats.

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In 2005, Dr. Christian P. Larsen, director of the Emory Transplant Center, Joseph B. Whitehead Professor and chair, Department of Surgery at Emory University School of Medicine, and Dr. Rafi Ahmed, Professor of Microbiology and Immunology at Emory and former director of the Emory Vaccine Center, received a biodefense contract to study protective immunity in transplant recipients. The five-year, $10.1 million contract consisted of three projects: (1) characterization of the impact of immunosuppression on immune memory, (2) exploring the impact of immunosuppression on the immune response to influenza vaccination, and (3) characterization of the immune response to vaccination challenge in immunosuppressed non-human primates. In 2009, Dr. Larsen and his colleagues received another two years of funding from the NIH to extend their long-standing P01 grant, "Interactions of Protective Immunity and Transplant Tolerance." This study expands the immunology lab's collaboration with Dr. Ahmed to develop new strategies for vaccination that can better protect organ transplant recipients and other immune-suppressed patients from infectious disease threats.

The P01 grant consists of three projects. In the first, Dr. Larsen will study the strategies and mechanisms by which donor specific tolerance could be induced. In the second, Dr. Alan  Kirk will study the host's relationship with herpes viruses, Epstein-Barr and cytomegalovirus, which cause significant morbidity after transplantation. For the third project, Dr. Ahmed will continue to study T cell memory and how it relates to pathogen development and is maintained in normal subjects and transplant recipients.

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