At the upcoming American Transplant Congress (ATC) 2023 in San Diego, CA, biotechnology company eGenesis will reveal groundbreaking data on xenotransplantation – the transplantation of living organs, tissues, or cells between species.
With these new insights into key molecular and cellular functions, the company is one step closer to their ultimate goal of providing human-compatible organs to those suffering from organ failure. Come 2023, eGenesis could usher in a revolutionary new era of clinical trials and treatment.
At ATC 2023, eGenesis proudly presented data showing their continued leadership in xenotransplantation. Thanks to their efforts, they have achieved successful long-term non-clinical transplants with engineered porcine donors.
Encouraged by their findings, they have now nominated a donor for clinical development with genome modifications that address hyperacute rejection, recipient compatibility, and the risk of zoonosis. With the highest aim of helping those in dire need of donor organs, the team at eGenesis eagerly awaits the prospect of advancing to clinical trials.
Oral Presentation: Genetically Modified Porcine Kidneys Expressing Human Transgenes Support >2-year Survival in Porcine Donor to Cynomolgus Macaque Recipient Xenotransplantation. Takayuki Hirose, MD, PhD, Research Fellow/Assistant Professor Transplant Surgery, Mass General Hospital / Department of Urology, Hokkaido University
Xenotransplantation presents a potential way to alleviate the serious organ shortage crisis, with recent developments in gene editing allowing for the introduction of genetic alterations which increase the compatibility and security of xenogeneic organs. Examples include xenoantigen elimination, human transgene expression, and retroviral inactivation. Ultimately, these efforts translate to improved transplants and better patient outcomes.
At eGenesis, scientists have developed an innovative way of ensuring successful organ transplantation by genetically engineering pig donors to carry specific modifications. Their groundbreaking triple knockout (3KO) process removes three xenoantigens known to cause hyperacute rejection and replaces them with seven human proteins involved in immunity.
To further bolster the transplant process, some donors are also undergoing a procedure to inactivate their porcine endogenous retrovirus. This cutting-edge procedure is revolutionizing organ transplantation and enabling safe, successful transplants.
Cynomolgus macaque recipients treated with porcine donor xenografts containing TGs showed a remarkable boost in survival compared to recipients who received xenografts with the 3KO; with a median survival time soaring from 24 days to 176 days. Furthermore, follow-up studies revealed that among those recipients, some even achieved long-term survival – with one outlasting for over two years and two making it 18 months. Adding to that, several more survived for over a year.
The porcine kidneys displayed remarkable filtration proficiency, with chemistry parameters that closely mirrored those of primates. This results were an impressive feat of nature!
Oral Presentation: Contribution of Anti-SLA Antibodies to Rejection in Nonhuman Primate Model of Kidney Xenotransplantation. William T. Serkin, Senior Research Associate, eGenesis, Inc.
In a startling revelation, a study of post-transplant blood serum samples collected from cynomolgus macaques revealed that only six out of fourteen recipients produced antibodies against SLA (swine leukocyte antigens), whereas the majority of anti-porcine antibodies in non-human primates appear to be directed at non-SLA antigens.
Even in animals with high levels of anti-porcine antibodies, SLA was not identified as the source of their immune reaction. This implies that SLA is not the only driving force behind antibody-mediated rejection (AMR), and thus raises important questions about the role of SLA in AMR.
Poster: Pre- and Post-Transplant Donor Specific Anti-Porcine Antibodies In Transplantation of Kidney Xenografts with Triple Knock-Out With or Without Multiple Human Transgenes in Nonhuman Primates. Ahmad Karadagi, Postdoctoral Research Fellow, Harvard Medical School / Massachusetts General Hospital
The prospect of successful xenograft survival is greatly improved through the introduction of porcine cells with three xenoantigen knockouts (3KO) and TGs (transplanted genes). Interestingly, pre-transplant levels of donor-specific anti-porcine antibodies (DSA) were not found to be associated with post-transplant survival.
Instead, the introduction of 3KO/TG xenokidneys significantly extended the survival of non-human primate recipients. Elevation of post-transplant DSA titers was however correlated with the occurrence of antibody-mediated rejection (AMR) and thrombotic microangiopathy (TMA). In recipients of 3KO only xenokidneys, graft losses were instead associated with acute tubular injury (ATI) and AMR.
About Transplantation and Xenotransplantation
Organ failure is a life-threatening and devastating condition, but thankfully, there is hope on the horizon. Transplantation is widely considered to be the gold standard treatment for organ failure, but unfortunately, the demand for organs vastly exceeds the supply. Of the more than 100,000 individuals in the US wait list for organ transplantation, only a fraction – around 40% – will be lucky to get a life-saving organ. The existing organ failure treatment paradigm is also far from perfect; it is limited by organ incompatibility and varying donor organ qualities. However, research and developments in medical technology is paving the way for better solutions.
Xenotransplantation – the transplantation of cells, tissues, and organs from one species to another – promises to be a promising solution to the long-standing problem of organ shortages facing the medical community. Recent advances in gene editing technologies, such as CRISPR, are providing groundbreaking solutions to the complicated virologic and immunologic problems that had hindered the progress of xenotransplantation for so long. This has created a beacon of hope for those waiting for a life-saving organ.
eGenesis is paving the way to create transplantable organs that are both safe and effective. Their technology is unique in that it manages both viral risk and molecular incompatibilities across different species. Not only have they achieved remarkable preclinical success, but they are actively developing programs to create solutions for acute liver failure, kidney transplant, and heart transplant. By merging the latest genome engineering technologies, eGenesis envisions a new horizon of hope for medical patients that desperately need organ transplants.