Advances in HLA desensitization for kidney transplant candidates

Human leukocyte antigen (HLA) sensitization is a significant barrier to kidney transplantation. The goal of HLA desensitization is to increase access to transplantation and reduce the risk of antibody-mediated rejection and graft loss. This review outlines currently used therapies and highlights novel strategies for HLA desensitization.

Important advances include promising data on imlifidase, a novel immunoglobulin G (IgG) endopeptidase that cleaves IgG molecules into Fc and F(ab)'2 fragments, negating antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). A positive phase III study will likely lead to FDA approval in December 2026. Additionally, initial reports of HLA desensitization using ant-CD38 monoclonal antibodies, bispecific T cell engagers targeting B-cell maturation antigen (BCMA), and chimeric antigen receptor T cells targeting CD19 and BCMA, suggest improved efficacy at HLA antibody reduction and lower risk of posttransplant DSA rebound.

Newer, more potent agents targeting pathogenic IgG molecules, B-cells and plasma cells are likely to improve the efficacy of HLA desensitization regimens. As data emerge from ongoing clinical trials, the clinical applicability of such therapies will depend, in addition to efficacy, on their safety profile, cost and complexity of use.