New CAR T treatment opens doors for kidney patients
An early trial demonstrates CAR T cells can safely desensitize even the most challenging transplant candidates.
A pioneering clinical trial has successfully enabled two patients with end-stage kidney disease to receive previously improbable kidney transplants. These individuals were considered among the most difficult in the nation to match with a compatible donor kidney due to harmful antibodies they had developed (“sensitized”). Researchers at the University of Pennsylvania (Penn) used chimeric antigen receptor (CAR) T-cell therapy, originally developed at Penn for treatment of blood cancer, to significantly reduce the level of harmful immune antibodies in these two highly sensitized patients, making kidney transplantation possible after years of waiting. The study’s findings appear today in the New England Journal of Medicine.
“This is the first demonstration that CAR T cells can be used not only to treat cancer, but also to help patients who previously had no opportunity to receive a compatible donor kidney,” said Ali Naji, MD, PhD, the Jonathan E. Rhoads Professor of Surgery and principal investigator of the study. “For patients who have spent years on the kidney transplant waiting list, this approach could be transformative.”
A critical challenge in kidney transplantation
More than 91,000 Americans are currently waiting for a kidney transplant. Among them, roughly 5,000 are “highly sensitized,” meaning their immune systems harbor extremely high levels of antibodies that would attack most donor kidneys. These antibodies are measured using a score called a Calculated Panel Reactive Antibody, or cPRA. Patients with a cPRA of 99.9 percent or higher are compatible with fewer than 1 in 1,000 donor kidneys and often must wait years for a suitable organ. In many cases, patients with extremely high cPRA scores never find a match. Traditional methods, such as a plasma exchange or drugs that try to block harmful antibodies, often fail in the most sensitized patients.
Repurposing CAR T therapy for transplant access
This Phase I clinical trial (NCT06056102)—a collaboration between researchers from Penn Medicine, NYU Langone, and Mass General—is the first to test whether dual CAR T-cell therapy, a treatment developed at Penn Medicine by Dr. Carl June and approved by the FDA in 2017 for treatment of blood cancers that reprograms a patient’s own immune cells, can safely remove the specific immune cells responsible for making anti-donor antibodies.
The experimental approach combines two engineered T‑cell therapies; CD19‑targeted CAR T-cells, which eliminate memory B cells, and BCMA‑targeted CAR T cells, which deplete antibody‑producing plasma cells. By removing both cell types, researchers aimed to markedly reduce circulating antibodies and effectively “reset” the immune system, enabling highly sensitized patients to receive donor kidneys that were previously incompatible. Two Penn Medicine patients with cPRA levels near 100%, each having spent years on transplant waitlists without a single viable match, underwent this CAR T‑based desensitization. Both experienced dramatic reductions in the harmful immune antibodies that typically attack donor kidneys, and their cPRA scores lowered enough to make new donor matches possible. As a result, both patients successfully received kidney transplants. To date, neither has shown signs of donor‑specific antibody rebound or organ rejection.
Minimal toxicity observed in early trial
“In this early trial, the CAR T-cell treatment was tolerated well, with no severe side effects, and the immune system began to recover as expected,” said study co-author Robert Montgomery, MD, PhD, the H. Leon Pachter, MD, Professor of Surgery, chair of the Department of Surgery at NYU Grossman School of Medicine, and director of the NYU Langone Transplant Institute. “This early success reflects what’s possible when teams across institutions push the boundaries of what cell therapy can do for transplant medicine. This treatment opens up new options for patients and could save thousands more lives every year.”
Notably, neither patient developed severe cytokine release syndrome or neurotoxicity, two complications that are sometimes observed in cancer patients treated with CAR T‑cell therapies. The depletion of immune cells was temporary, as healthy B‑cell populations gradually recovered over time. Future phases of the trial will study higher doses of CAR T cells and enroll a larger group of patients to further assess safety, durability, and overall effectiveness.
A second chance at life… again
For more than four decades, Philadelphia resident Andrew Boyd has lived with kidney disease. At age 14, sudden swelling throughout his body led to a diagnosis of focal glomerulosclerosis, which is scarring of the part of the kidney that filters blood. Kidney failure followed soon after. At age 14, he received his first transplant in 1993 at the Children’s Hospital of Philadelphia. His second kidney transplant was in 2009, at the Hospital of the University of Pennsylvania. But by 2018, as his second transplant began to fail, and his antibody levels climbed to nearly 100 percent, it became clear that receiving a third kidney would be nearly impossible. “I tried to stay hopeful,” Boyd said, “but there were days I wondered if a third transplant would ever come.”
That changed when Boyd volunteered to participate in Penn Medicine’s pioneering study using CAR T-cell therapy to lower antibody levels in highly sensitized kidney patients. Beginning in early 2025, he underwent months of lab work, cell collection, and treatment, all while continuing the dialysis that was essential for him to stay alive. Within weeks of receiving his engineered immune cells back, his antibody levels began to fall. By August, Boyd, at age 47, received the news he once thought impossible: a viable kidney match had been found, and he received his third transplant at Penn Medicine.
Now more than nine months post‑transplant, Boyd reflects on the hard work of the researchers, doctors, surgeons, and care teams at Penn. “To have this kind of innovation happening right in my backyard at Penn—it’s hard to put that gratitude into words,” he said. “I’m here today because a team believed in me, fought for me, and pushed science forward. They gave me a second chance at life…. again.”
“The success of this trial underscores the extraordinary caliber of science at Penn and the power of cross-disciplinary collaboration, exemplified by the contributions of Mary Kaminski, PA-C and Kyle Jackson MD, PhD, from Penn Transplant Surgery, Vijay Bhoj, MD, Malek Kamoun MD, PhD, and Nicholas Brown PhD from Penn Pathology, Sabiha Hussain, MD of Penn Nephrology, and Alfred Garfall, MD from Penn Hematology and Oncology. We are grateful for the leadership and advice of our colleagues at National Institute of Allergy and Infectious Diseases (NIAID) in the implementation of this multicenter novel therapy to facilitate successful kidney transplantation,” said Naji.
This study was made possible through support from Penn’s Center for Cellular Immunotherapies, the Gift of Life Donor Program, and the organ donors and their families. The study is funded by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (U01‑AI163087) as part of the Clinical Trials in Organ Transplantation Consortium. Additional funding comes from Blood Cancer United and the Burroughs Wellcome Fund.
Editor’s note: The content in this release is solely the responsibility of the University of Pennsylvania and does not necessarily represent the official views of the National Institutes of Health.
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