CAR T Cell Therapy Enables Kidney Transplants in Highly Sensitized Patients in First-of-Its-Kind Trial
核心洞察
A pioneering phase 1 clinical trial used dual CAR T cell therapy (CD19 (搜索) and BCMA (搜索)-targeted) to successfully desensitize three highly sensitized end-stage kidney disease (搜索) patients, enabling previously impossible kidney transplants.
The study, published in The New England Journal of Medicine, marks the first demonstration that CAR T cells can be used outside oncology to eliminate antidonor antibodies and reset the immune system.
Neither of the first two treated patients developed severe cytokine release syndrome or neurotoxicity, and healthy B cell populations gradually recovered after temporary depletion.
A groundbreaking phase 1 clinical trial has demonstrated that chimeric antigen receptor (CAR) T cell therapy—originally developed to treat blood cancers—can safely desensitize even the most challenging kidney transplant candidates, enabling three patients with end-stage kidney disease (搜索) to receive previously improbable kidney transplants. The findings were published June 4 in The New England Journal of Medicine.
The trial (NCT06056102), a collaboration between researchers at Penn Medicine (搜索), NYU Langone Health, 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 received FDA approval in 2017 for 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 (搜索). "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 calculated panel reactive antibody (cPRA) score. Patients with a cPRA of 99.9% 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 plasma exchange or drugs that attempt to block harmful antibodies, often fail in the most sensitized patients.
Dual-Target CAR T Strategy
The experimental approach combines two engineered T cell therapies: CD19-targeted CAR T cells (搜索), which eliminate memory B cells, and BCMA-targeted CAR T cells (搜索), 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 (搜索) patients with cPRA levels near 100%, 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.
Safety Profile and Immune Recovery
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.
"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 NYU Grossman School of Medicine, chair of the Department of Surgery, 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."
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 Patient's Journey
Brittney Patterson, 38, has been on and off a dialysis machine since she was 11 years old. She overcame multiple health challenges, including two failed kidney transplants, since first being diagnosed with kidney disease as a child. Her cPRA had risen to 99.9%, and she spent 21 years on dialysis. During those decades, she developed renal osteodystrophy (搜索), which caused weakness in her hips and shoulders, requiring a total left hip replacement in 2011.
After joining the kidney waitlist with the NYU Langone Transplant Institute in January 2025, Patterson learned about the CAR T cell therapy clinical trial and enrolled. She received CAR T cell infusion therapy through the 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 NYU Langone Transplant Institute, monitored her antibody levels and side effects for several months. After her antibody levels reduced, a matching kidney became available, and she received a transplant on May 15 by Dr. Montgomery.
"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 reflected: "My story is not just about receiving a kidney transplant. It is about perseverance, hope, and the incredible possibilities that can emerge when medicine, innovation, and determination come together."
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, with additional funding from Blood Cancer United and the Burroughs Wellcome Fund. Massimo Mangiola, PhD, director of NYU Langone's Immunogenetics Laboratory, assisted in analyzing changes in antibody levels and co-authored the study.