Modified donor blood cells seem a promising option in kidney transplant recipients

Transfusion of modified donor blood cells into kidney transplant recipients results in donor-specific unresponsiveness which is long lasting and associated with a striking increase in IL-1-producing regulatory B lymphocytes (B_reg). Donor-specific unresponsiveness was abolished in vitro after B lymphocyte depletion, suggesting a direct pathophysiological role for B_reg [1].

Administration of modified immune cells prior to kidney transplantation resulted in specific immunosuppression against the allogeneic donor and a significant increase in B_reg [2]. Dr Matthias Schaier (Heidelberg University, Germany) explained that he and his team investigated how this approach affects the clinical course of treated patients. “We compared the clinical outcomes of 10 patients from a phase 1 clinical trial who had received modified immune blood cell infusions before kidney transplantation to the results of 15 matched standard-risk recipients. Follow-up was until year 5 after surgery.” The 10 patients who received modified immune blood cell infusions showed an excellent clinical course with stable kidney graft function and showed no donor-specific human leukocyte antigen antibodies or acute rejections during follow-up. In the other group, 1 of the patients died, and 5 developed donor-specific human leukocyte antigen antibodies. Opportunistic infections were reported more frequently in the control group than in those receiving modified immune blood cell infusion. Dr Schaier mentioned that based on these findings, modified donor blood cells may be a useful tool for the targeted induction of tolerogenic B_reg. “Also, a phase 2 study is underway to test the hypothesis that modified donor blood cell infusions lead to an operational tolerance-like phenotype [1].”

1. Schaier M, et al. Five-Year Follow-Up of a Phase 1 Trial of Donor-Derived Modified Immune Cell Infusion in Kidney Transplantation. SA-OR47, ASN Kidney Week 2022, 3–6 Nov.
2. Morath C, et al. J Clin Invest 2020;130:2364–2376.

 

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Posted on 8 December 2022