Dual CAR T-Cell Therapy Enables Kidney Transplantation in Highly Sensitized Patients

A dual chimeric antigen receptor (CAR) T-cell therapy enabled kidney transplantation in two highly sensitized patients by reducing anti-HLA antibodies that previously limited their access to compatible donor organs, according to findings from an early multicenter phase 1 study published in the New England Journal of Medicine.

The ongoing study is evaluating a combination of CD19-targeted and B-cell maturation antigen (BCMA)-targeted CAR T cells in kidney transplant candidates with calculated panel-reactive antibody (cPRA) scores of 99.9% or higher. The cPRA score estimates the percentage of potential organ donors with whom a candidate would be incompatible because of preexisting anti-HLA antibodies — meaning these patients would be unlikely to find a suitable donor through conventional allocation pathways. The approach was designed to eliminate memory B cells and plasma cells that produce those antibodies, offering a potential new desensitization strategy for patients with few transplant options.

Both patients in the study's safety run-in cohort experienced reductions in anti-HLA antibody levels following treatment, allowing investigators to remove selected unacceptable antigens from their transplant listings and lower their cPRA scores. The patients subsequently received crossmatch-compatible kidney transplants.

No donor-specific antibody rebound was observed during the reported follow-up period, and neither patient experienced high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, although transient cytopenias occurred in both patients. Notably, patients in the safety run-in cohort received CAR T-cell doses that were one-tenth those used in previous oncology studies, along with a milder lymphodepleting chemotherapy regimen.

The authors emphasized that the phase 1 study is ongoing, with additional cohorts planned to evaluate higher CAR T-cell doses and intensified lymphodepleting regimens. If the safety and efficacy of the approach are confirmed in larger studies, dual CAR T-cell therapy may represent a new desensitization strategy for highly sensitized transplant candidates and further expand the use of cellular therapies beyond oncology.