Tim Andrews, 67, has now lived more than eight months with a genetically-engineered pig kidney, making him the longest-living human recipient of such an organ to date.
Discharged from dialysis and thriving, he stands at the vanguard of a shift in transplantation science. At the same time, biotechnology firm eGenesis has just won FDA clearance to begin a full clinical trial of its porcine kidney candidate EGEN-2784. Together, these developments mark what may be a turning point with xenotransplantation no longer being speculative science, but a nascent therapy entering human trials.
For decades, xenotransplantation — transplanting organs across species, typically pig to human — was seen as a scientific dream fraught with immunologic, viral, and ethical obstacles. But over the past 10 years, advances in gene editing, immunosuppression, and surgical techniques have gradually narrowed the chasm between possibility and practice. What once seemed limited to science fiction may now inch toward clinical reality.
A decade of progress
In the early 2010s, pig-to-primate grafts produced promising but short-lived results, hampered by hyperacute rejection, coagulation mismatch, and immunologic injury. Researchers experimented with deleting pig antigen genes, adding human “protective” transgenes, and suppressing complement cascades.
Over time, multi-gene edited pigs emerged. These were animals engineered to lack key xenoantigens, express human regulators, and in some cases suppress endogenous retroviruses (ERVs) to reduce viral risk. eGenesis itself has reported generating piglets free of active porcine ERVs (PERVs) and combining that with additional edits to improve immune compatibility.
With this improved donor biology, immune suppression became the next frontier. Conventional transplant immunosuppressants — broad-spectrum agents that deplete or cripple lymphocytes — were known to carry risks including nephrotoxicity, hypertension, diabetes, infections, and non-specific immune suppression. This posed a challenge: how to block rejection without compromising the patient.
By the early 2020s, the field began shifting toward costimulation blockade — interfering with the communication between immune cells rather than simply removing them. The CD40–CD40L (cluster of differentiation 40–cluster of differentiation 40 ligand) axis, in particular, gained attention. A number of anti-CD40L antibodies had once been tested, but early versions triggered thromboembolic events due to the formation of immune complexes activating platelets. In response, newer designs of antibodies, like tegoprubart, were engineered to reduce binding to platelet receptors while retaining high affinity for CD40L, aiming to preserve immunologic suppression without clotting risk.
In parallel, surgical teams improved organ procurement, perfusion, and implantation techniques. Transplant centers began to assemble multi-disciplinary xenotransplant teams combining gene editing, immunology, surgery, and regulatory coordination.
By the mid-2020s, pig-to-human cases under compassionate or expanded access started emerging. Those cases became testbeds for real-world lessons in rejection, immune modulation, and post-surgical care.
Refining the approach
At its core, the barrier to xenotransplantation is immunologic.
A pig kidney is foreign in multiple dimensions: cell-surface antigens, complement regulators, coagulation mediators, and viral signatures. The human recipient’s immune system sees the graft as a threat and mounts a multifaceted attack — resulting in the activation of antibodies, T cells, macrophages, complement cascade, coagulation, and inflammatory activity against the transplanted organ.
Standard-of-care immunosuppressive regimens, like calcineurin inhibitors, blunt immune responses largely by depleting or inactivating broad classes of immune cells. By contrast, tegoprubart’s mechanism is subtler and more selective. The antibody blocks CD40L, a co-stimulatory ligand expressed on T cells and other immune cells. That blockade interrupts the second signal required for T-cell activation, B-cell help, dendritic cell maturation, and cross-talk among immune populations. This does not kill large swaths of immune cells; rather, it dampens their communication and activation potential. Blocking CD40L also helps polarize some lymphocytes into regulatory T cells that suppress immune response.
Because rejection involves multiple cell types — helper T cells, NK cells, B cells, antigen-presenting cells — this co-stimulation blockade is conceptually more precise. In effect, it's an immunologic brake rather than a sledgehammer.
In pig-to-primate and nonhuman primate (NHP) kidney transplant models, anti-CD40L regimens have consistently extended graft survival, particularly when paired with complement inhibitors and adjunct therapies. In published work, tegoprubart monotherapy produced long-term graft success in NHP islet and kidney models without overt thromboembolic complications.
In human kidney allotransplant trials, tegoprubart has advanced into Phase 1b and Phase 2 settings. One registrational trial, named BESTOW, compares tegoprubart directly against another immunosuppressive drug, tacrolimus, with endpoints including eGFR (estimated glomerular filtration rate) which assesses kidney function rejection rate, new-onset diabetes, and graft survival. Early safety data and tolerability from other ndications, such as amyotrophic lateral sclerosis (ALS), report no signal of major thrombotic events. Based on the latest data reported from the Phase 1b study in kidney allotransplant, tegoprubart continues to be well tolerated.
This shift, from blanket immune suppression to modulation of signaling, reflects a maturing transplant immunology paradigm.
From pig to patient
After many years of testing and tailoring xenotransplant approaches, the stage was set to finally move into humans. At Massachusetts General Hospital (MGH), three patients have now received engineered porcine kidneys under expanded-access protocols. The first was Andrews, who received his kidney transplant on January 25, 2025, and has remained off dialysis over eight months post-surgery. The third, Bill Stewart, received his transplant on June 14, 2025, and was discharged from the hospital one week later.
These procedures did not rely on standard immunosuppressive regimens alone; they incorporated tegoprubart as a key component of the immunologic regimen, alongside complement inhibition and other conventional therapies. The survival of Andrews, now the longest-living recipient of a genetically-engineered pig kidney, suggests that the combination of gene editing and targeted immunosuppression is carrying forward to other patients.
Leonardo Riella, Medical Director for Kidney Transplant at MGH, and lead surgeons Tatsuo Kawai and Nahel Elias emphasized in the press release that bringing these cases to life required extensive cross-sector collaboration — from biotech, hospitals, government, and regulatory agencies.
Though ambitious, these two human cases build from a foundation of nonhuman primate data, gene-editing techniques, and refined immunology. Each human subject is a deliberate experiment, an opportunity to test safety, durability, and mechanistic assumptions in real physiology.
It’s worth noting a counterpoint: In the recent pig-to-human kidney transplant of Towana Looney, which did not involve tegoprubart, the graft functioned for about four months before being removed due to rejection, underscoring that setbacks remain part of progress.
What this means for broader transplantation
Beyond xenotransplantation itself, the implications of these advances ripple into conventional human-to-human transplant practice. Tegoprubart is already being trialed in human kidney allotransplant settings through BESTOW and has been tested in islet transplantation in type 1 diabetes protocols at the University of Chicago, where the first three recipients achieved insulin independence. The same logic — blocking co-stimulatory signaling rather than destroying immune cells — could reduce side effects like hypertension, diabetes, nephrotoxicity, and tremors associated with longstanding immunosuppressants.
If xenografts become durable, safe, and scalable, they may allow transplant programs to expand access to organs, reduce waitlists, and tackle disparities in donor availability. Human-to-human transplant centers may adopt hybrid models, combining costimulation blockade with milder maintenance immunosuppression — particularly in sensitized or high-risk patients. The engineering lessons from eGenesis’ multi-gene edited pigs may also inform donor organ optimization more broadly.
Too soon to tell?
The xenotransplantation field remains in its early days. The human cases are few, results are preliminary, and long-term durability and safety are unproven.
But one thing is for sure: Xenotransplantation is no longer purely theoretical. The combination of advanced gene editing and smarter immunosuppression (e.g., CD40L blockade) is pushing the field toward real, sustained applicability. If these technologies succeed, the promise is immense, nothing short of an expanded supply of transplantable organs, reduced waitlist deaths, and a fundamental shift in how we treat organ failure.
And while the barriers remain steep, with regulatory approvals, long-term safety, economic viability and manufacturing pipelines still to be addressed, the next few years — and the success of trials like BESTOW and further xenograft recipients — will determine whether this is a leap or a mirage.
