Winning Solution: Alemtuzumab Induction Therapy In Monkeys With Life-supporting Pig Kidney Transplants
Experts in (i) immunosuppressive therapy and/or (ii) pig organ transplantation research improve the immunosuppressive regimen in pig-to-human kidney transplantation
David Cooper, MD, PhD, FRCS, Massachusetts General HospitalContact
Artificial Kidney Prize, Phase 2: Track One
David Cooper, MD, PhD, FRCS
About the Solution
There is an urgent need for improved therapy for patients with kidney failure to provide them with a better quality and a longer length of life than is possible on dialysis. The pig kidney is a ‘ready-made’ replacement for a human kidney and will possibly never be matched by any ‘artificial kidney’, i.e., by a mechanical or biomechanical device. Recent data (largely from my own group while supported in part by a Kidney X Phase 1 Prize) indicate that a pig kidney will fulfill all the essential functions of a human kidney.
The major barrier to successful pig kidney transplantation in humans or nonhuman primates (NHPs) is rejection of the kidney. A kidney from a wild-type pig, i.e., a pig that has not undergone any genetic modifications, transplanted into a NHP, e.g., a baboon (that has a similar rejection response to that of a human recipient) is rejected usually within minutes or hours. However, if the pig is genetically-modified (by deleting the pig targets for the initial human rejection response, and by introducing human ‘protective’ genes), pig kidney graft survival in immunosuppressed NHPs can currently be maintained in some cases for >1 year.
Conventional immunosuppressive regimens used in the transplantation of human organs have been demonstrated to be ineffective in preventing rejection of pig kidney grafts. This barrier has been partially overcome by novel immunosuppressive agents that are not yet approved by the US Food and Drug Administration (FDA) for administration to patients. Although this has greatly prolonged kidney graft survival in NHP recipients, the results are not yet consistent enough to warrant initiation of a clinical trial. Improved efficacy of the immunosuppressive regimen is required.
A panel of experts in (i) immunosuppressive therapy and/or (ii) pig organ transplantation research was convened to advise on improving the immunosuppressive regimen in pig kidney transplantation. The regimen they recommended will be tested when genetically-modified pig kidneys are transplanted into baboons. The FDA requires follow-up of pig organ transplantation in NHPs to be for 12 months, during which period the recipient’s rejection response will be carefully monitored. It is anticipated that the results of the proposed study will be sufficiently successful to satisfy the FDA that a limited clinical trial of pig kidney transplantation in patients can be initiated.
These studies will hopefully eventually enable all patients awaiting a kidney transplant to undergo a pig kidney transplant whenever required, obviating the need for dialysis to be carried out for years until a kidney from a deceased human donor becomes available.
About the Winner
David K. C. Cooper, MA, MS, MD, PhD, DSc (Med) studied medicine in the UK at Guy’s Hospital Medical School (now part of King’s College London), and trained in general and cardiothoracic surgery in Cambridge and London. Between 1972 and 1980, Dr. Cooper was a Fellow and Director of Studies in Medical Sciences at Magdalene College, Cambridge. In 1980, Dr. Cooper took up an appointment in cardiac surgery at the University of Cape Town where, under Professor Christiaan Barnard, he had responsibility for patients undergoing heart transplantation. In 1987, Dr. Cooper relocated to the Oklahoma Transplantation Institute where he continued to work in both the clinical and research fields.
After 17 years as a surgeon-scientist, Dr. Cooper decided to concentrate on research, initially at the Massachusetts General Hospital/Harvard Medical School in Boston (1996-2005, to which center he returned in 2021), and subsequently at the University of Pittsburgh (2005-2016), and the University of Alabama at Birmingham (2016-2021). Dr. Cooper’s major interest is in developing cross-species transplantation with the aim of using pigs as sources of organs, cells, and corneas for transplantation in humans.