HLA Sensitization

This study is a prospective, open-label, two-arm exploratory clinical trial aimed at evaluating the safety and efficacy of Bispecific T-cell Engager (BiTE) therapies in refractory, highly sensitized kidney transplant candidates. Patients with end-stage renal disease (ESRD) who have a calculated panel reactive antibody (cPRA) ≥ 90% and have waited for a transplant for over 5 years, despite receiving standard desensitization therapies (e.g., IVIG, plasmapheresis, rituximab), will be enrolled. A total of 20 participants will be randomized in a 1:1 ratio to receive either Blinatumomab (a CD19×CD3 BiTE) or Teclistamab (a BCMA×CD3 BiTE). The primary objective is to evaluate the desensitization response rate, defined as the reduction of cPRA to \< 20% or by ≥ 50% from baseline, assessed at multiple time points up to 1 year post-treatment. Secondary objectives include assessing the safety profile (such as the incidence of Cytokine Release Syndrome \[CRS\] and neurotoxicity), the extent of CD19+ B cell depletion, and the proportion of participants who successfully undergo kidney transplantation within 1 year.

The purpose of this clinical trial is to evaluate whether a temporary reprogramming of the immune system can help highly sensitized (hyperimmunized) patients with end-stage kidney disease safely receive a compatible kidney transplant. Patients who are highly sensitized have developed an extremely high level of antibodies against human leukocyte antigens (HLA), often due to previous transplants, pregnancies, or blood transfusions. This condition makes it nearly impossible for them to find a compatible organ donor, leaving them stuck on dialysis indefinitely. This study tests an innovative strategy using Autologous Hematopoietic Stem Cell Transplantation (AHSCT). The procedure involves an intensive conditioning regimen using a combination of medications (cyclophosphamide, thymoglobulin, and rituximab) to deeply clear out the patient's existing mature immune cells. This is followed by the reinfusion of the patient's own previously collected and purified blood stem cells (CD34+ cells) to rebuild the immune system from scratch. The investigators hypothesize that this procedure will eliminate the "immunological memory" cells responsible for producing the problematic anti-HLA antibodies, resetting the immune system to a "naive" or inactive state. This immune reset is expected to eliminate or significantly lower circulating HLA antibodies, creating a critical window of opportunity for these patients to successfully receive a compatible kidney transplant from the deceased-donor waiting list.