June 03, 2026 —
Researchers at the University of Pennsylvania reported that CAR-T cell therapy enabled two highly sensitized patients with end-stage kidney disease to receive kidney transplants after years of being considered extremely difficult to match with compatible donor organs.
The findings, published in The New England Journal of Medicine, describe a Phase 1 clinical trial evaluating whether CAR-T therapy could reduce harmful anti-donor antibodies in patients with very high immune sensitization. These patients had cPRA scores near 100%, meaning they were compatible with fewer than one in 1,000 donor kidneys and had spent years on transplant waiting lists without viable matches.
Highly sensitized patients develop antibodies that can attack most donor kidneys, making transplantation extremely difficult. Traditional desensitization strategies, such as plasma exchange or antibody-blocking drugs, often fail in the most sensitized cases. The new study tested whether CAR-T therapy could more directly remove the immune cells responsible for producing these antibodies.
The experimental approach used a dual CAR-T strategy combining CD19-targeted CAR-T cells and BCMA-targeted CAR-T cells. CD19 CAR-T cells are designed to eliminate memory B cells, while BCMA CAR-T cells target antibody-producing plasma cells. By depleting both populations, researchers aimed to reduce circulating anti-donor antibodies and effectively reset the immune environment enough to allow transplantation.
Both treated patients experienced major reductions in harmful immune antibodies, lowering their cPRA scores enough to identify compatible kidney donors. As a result, both successfully received kidney transplants. To date, neither patient has shown signs of donor-specific antibody rebound or organ rejection.
The treatment was also reported to be well tolerated in this early study. Neither patient developed severe cytokine release syndrome or neurotoxicity, complications sometimes associated with CAR-T therapy in oncology. Immune-cell depletion appeared temporary, with healthy B-cell populations gradually recovering over time.
Although the study remains early and involved only two patients, it represents an important proof of concept for applying CAR-T therapy beyond cancer. Future phases of the trial will evaluate higher CAR-T doses and enroll more patients to better assess safety, durability, and effectiveness.
If further validated, this approach could open a new path for highly sensitized kidney transplant candidates who currently have few or no realistic transplant options.
