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A pioneering clinical trial has successfully enabled three 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. Researchers at 91����Ƶ Langone Health and the University of Pennsylvania used chimeric antigen receptor (CAR) T cell therapy, originally developed to treat blood cancer, to significantly reduce the levels of harmful immune antibodies in highly sensitized patients, making kidney transplantation possible after years of waiting. The study’s findings were published June 4 in The New England Journal of Medicine.

“In this early report, which describes the first two patients, 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, DPhil, the H. Leon Pachter, MD, Professor of Surgery at 91����Ƶ Grossman School of Medicine, chair of the , and director of the 91����Ƶ 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.”

This phase 1 clinical trial (NCT06056102)—a collaboration between researchers from Penn Medicine, 91����Ƶ Langone, and Massachusetts General Hospital—is the first to test whether dual CAR T cell therapy can safely remove the specific immune cells responsible for making antidonor antibodies. The treatment, which reprograms a patient’s own immune cells, was developed at Penn Medicine by Carl H. June, MD, and approved by the Food and Drug Administration in 2017 for the treatment of blood cancers.

“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 the study’s lead author and principal investigator, Ali Naji, MD, PhD, the Jonathan E. Rhoads Professor of Surgery at Penn Medicine. “For patients who have spent years on the kidney transplant waitlist, 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 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 predicted on average to receive only one offer for every 10 years of waiting on the list. 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

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. The study included two Penn Medicine patients with cPRA levels near 100 percent, both of whom spent years on transplant waitlists without a single viable match. After undergoing 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, they successfully received kidney transplants. To date, neither has shown signs of donor‑specific antibody rebound or organ rejection.

Notably, neither patient developed severe cytokine release syndrome or neurotoxicity, two complications that are sometimes observed in cancer patients treated with CAR T cell therapy. 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 New Chance at Life

Brittney Patterson, 38, has been on and off a dialysis machine since she was just 11 years old. She has overcome a variety of health challenges, including two failed kidney transplants, since she was first diagnosed with kidney disease as a girl. Today, she is one of three people with nearly 100 percent antibody levels who got a new kidney following this CAR T cell therapy clinical trial protocol. She received a transplant after the New England Journal of Medicine manuscript was under review.

“I’m proud of myself for sticking it out through all of my setbacks,” she said. “I’m happy and I’m feeling great. My body feels good. My skin looks brighter. My eyes are bright and clear. It’s been a whole big change, and I’m just so grateful.”

Patterson, who has worked as a phlebotomist for the past 12 years, has a dialysis machine at home and had grown accustomed to using it just about every day for decades. She became an expert at cannulating herself by age 15. Being dependent on the machine has limited some of her options in life, but now she says she’ll be able to go back to school to realize her dream of becoming a nurse.

Her transplant journey started in 2000, when her mom donated one of her kidneys to her. Unfortunately, an undetected disease in the donor kidney reactivated a few years later, and the kidney failed in 2005. Another attempt at a kidney transplant that same year from a deceased donor failed due to clotting during surgery.

At that point, Patterson’s cPRA had risen to 99.9 percent, so she spent 21 years on dialysis. During those decades, she developed renal osteodystrophy, which caused weakness in her hips and shoulders. She underwent a total left hip replacement in 2011.

After joining the kidney waitlist with the 91����Ƶ Langone Transplant Institute in January 2025, she learned about the CAR T cell therapy clinical trial and enrolled. She had CAR T cell infusion therapy through Blood and Marrow Transplantation and Cellular Therapy Center, part of Perlmutter Cancer Center, on December 8, 2025. The study team, including Nicole M. Ali, MD, medical director of kidney transplantation for the 91����Ƶ Langone Transplant Institute, monitored Patterson’s antibody levels and side effects for several months following the therapy. After her antibody levels reduced, a matching kidney came last month. She received a transplant on May 15 by Dr. Montgomery and is now back home in New Jersey.

“We are thrilled to see Brittney finally put dialysis behind her and be able to receive a new kidney thanks to this therapy,” said Dr. Ali. “There are so many patients with difficult matching criteria, and we’re hopeful this therapy will become a routine option for others like her.”

Patterson is now reflecting on her journey and all the hardships that led to this moment.

“My story is not just about receiving a kidney transplant,” she said. “It is about perseverance, hope, and the incredible possibilities that can emerge when medicine, innovation, and determination come together.”

Massimo Mangiola, PhD, director of , assisted in analyzing changes in the antibody levels and co-authored the study.

The study is funded by grant U01‑AI163087 from the National Institute of Allergy and Infectious Diseases as part of the Clinical Trials in Organ Transplantation Consortium. Additional funding comes from Blood Cancer United and the Burroughs Wellcome Fund.

The content is solely the responsibility of 91����Ƶ Langone and does not necessarily represent the official views of the National Institutes of Health.

About 91����Ƶ Langone Health

91����Ƶ Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked 91����Ƶ Langone No. 1 out of 118 comprehensive academic medical centers across the nation for four years in a row, and U.S. News & World Report recently ranked four of its clinical specialties No. 1 in the nation. 91����Ƶ Langone offers a comprehensive range of medical services with one high standard of care across seven inpatient locations, its Perlmutter Cancer Center, and more than 320 outpatient locations in the New York area and Florida. The system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise.

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