A Phase I trial from Penn, NYU Langone, and Mass General tested dual CAR T-cell therapy to desensitize highly sensitized kidney patients, enabling donor kidney transplants that were previously unlikely.

Two Penn Medicine patients with near-100% cPRA scores showed dramatic reductions in antidonor antibodies and obtained compatible donor kidneys; both have not shown donor-specific antibody rebound or organ rejection so far.

The study, published in The New England Journal of Medicine on June 4, details two initial patients and a third later, all of whom received kidney transplants after CAR T-cell–based desensitization that reduced anti-donor antibodies and cPRA scores.

The trial design minimizes severe adverse events such as cytokine release syndrome or neurotoxicity, and B cell populations recovered gradually after treatment; higher dose cohorts and more patients will be studied in future phases.

The trial involves a collaboration among Penn Medicine, NYU Langone, and Mass General, and is supported by NIH funding (U01-AI163087) and other institutional sources; future phases will explore higher CAR T doses and more patients to assess safety, durability, and effectiveness.

The study is supported by Penn's Center for Cellular Immunotherapies, Gift of Life Donor Program, NIAID NIH funding, and additional funding from Blood Cancer United and the Burroughs Wellcome Fund.

The research is a collaboration among Penn Medicine, NYU Langone, and Massachusetts General Hospital, led by Ali Naji, MD, PhD (Penn Medicine) and supported by funding from the National Institute of Allergy and Infectious Diseases as part of the Clinical Trials in Organ Transplantation Consortium, along with other sponsors.

First author and study leaders emphasize this demonstrates CAR T cells can help patients achieve transplant access, potentially transforming outcomes for thousands on waiting lists.

Broader context: This work exemplifies translating CAR T-cell technology from oncology into transplant immunology, reflecting Penn Medicine’s leadership in cellular therapies and collaborative translational research.

Safety and tolerability: Treatments were generally well-tolerated in kidney patients, with transient B cell and plasma cell depletion and manageable safety profiles, differing from some cancer CAR T-cell therapies in adverse events.

Source and references: Findings published in the New England Journal of Medicine; clinical trial registered as NCT06056102; related references and institutional press materials.