In kidney transplantation, the primary challenge for certain patients is not merely finding a suitable organ, but selecting a donor whose tissue will not be rejected by their body through an acute immune response.
At times, this immune barrier is so formidable that it renders transplantation virtually impossible. It is precisely this difficult, seemingly dead-end problem that researchers from the Medical University of Vienna highlight in a new clinical report published in the New England Journal of Medicine.
The authors present the case of a highly sensitized patient for whom the chance of transplantation using conventional medical approaches was practically nonexistent. However, a recent scientific breakthrough fundamentally altered the situation.
A Long Wait and a Nearly Hopeless Condition
The patient was a 37-year-old male who had been on long-term dialysis. He had already experienced two failed kidney transplant attempts and had spent more than 12 years on the donor waiting list. His immune profile further complicated matters: his calculated Panel Reactive Antibody (cPRA) score reached 100%, and the probability of finding an ABO-compatible donor was virtually zero. This meant that traditional matching methods left almost no hope of locating a suitable organ.
This represents the exact category that concerns transplantation specialists most: patients whose immune systems have become so hyper-sensitized that even if an organ becomes available, the risk of rejection is extremely high, while the pool of compatible donors remains extraordinarily small. Existing desensitization methods, despite isolated successes, often yield only partial and temporary results.
A Different Approach to Desensitization
The Viennese medical team approached the problem from an entirely different angle. Rather than attempting to suppress the immune response solely through conventional methods, they administered the drug teclistamab over a period of 31 weeks, beginning in July 2024. The primary targets of the medication were the B cells and plasma cells responsible for producing the specific harmful antibodies that impede transplantation.
Teclistamab is a bispecific, BCMA-directed T-cell engaging therapy originally developed to treat hematologic malignancies. In this specific clinical case, it demonstrated a fundamental outcome—sharply reducing HLA antibody levels. Furthermore, undifferentiated, transitional, and memory B cells, as well as plasmablasts and plasma cells, were rapidly depleted in the blood and bone marrow. The treatment also diminished reactivity toward blood groups (ABO system) and reduced levels of anti-galactose-alpha-1,3-galactose xenoantibodies.
Along with the sharp reduction in antibody burden, the patient’s condition changed fundamentally. Once specific HLA antigens were excluded from his profile, the likelihood of a compatible donor appearing rose from zero to 1.35%. The first kidney offer was received in February 2025, but the surgery could not proceed due to technical reasons; shortly thereafter, in March 2025, the patient was involved in an accident while riding an e-scooter and required hospitalization, leading to the discontinuation of teclistamab therapy.
Nevertheless, a second organ offer in July 2025 was followed by a successful transplantation. At that stage, donor-specific antibodies were no longer detectable in the patient, and deep immunological analysis confirmed a critical drop in HLA antibody titers. As noted in the medical report, the patient’s kidney function is ideal today, and he no longer requires dialysis.
Why This Case Matters
The significance of this clinical success lies not in the immediate establishment of a new universal standard, but in opening a distinct perspective on desensitization. According to the authors’ assessment, BCMA-directed therapy could represent a breakthrough step for highly sensitized patients—a challenging group for whom conventional therapeutic strategies are frequently powerless.
However, alongside the achieved success, the treatment carried certain risks. The use of teclistamab triggered mild cytokine release syndrome, transient cytomegalovirus and BK virus viremia, urinary tract infections, and hypogammaglobulinemia, which necessitated intravenous immunoglobulin therapy. These complications serve as a reminder to clinicians that such large-scale modulation of the immune system leaves the body temporarily vulnerable to infectious agents.
What Comes Next
Although the potential future applications of this method generate great interest, they remain at a hypothetical level for now. The authors suggest that a similar strategy could, over time, play a key role in xenotransplantation, ABO-incompatible transplantations, heart transplantation, and even in the treatment of post-transplant antibody-mediated rejection. Nevertheless, they emphasize that these avenues require rigorous and large-scale studies before being implemented into broad clinical practice.
Source:NEJM
