Imlifidase Desensitization in HLA-incompatible Kidney Transplantation: Finding the Sweet Spot

Abstract

Imlifidase, derived from a Streptococcus pyogenes enzyme, cleaves the entire immunoglobulin G pool within hours after administration in fully cleaved antigen-binding and crystallizable fragments. These cleaved fragments can no longer exert their antibody-dependent cytotoxic functions, thereby creating a window to permit HLA-incompatible kidney transplantation. Imlifidase is labeled, in Europe only, for deceased donor kidney transplantation in highly sensitized patients, whose chances for an HLA-compatible transplant are negligible. This review discusses outcomes of preclinical and clinical studies on imlifidase and describes the phase III desensitization trials that are currently enrolling patients. A comparison is made with other desensitization methods. The review discusses the immunological work-up of imlifidase candidates and especially the “delisting strategy” of antigens that shift from unacceptable to acceptable with imlifidase desensitization. Other considerations for clinical implementation, such as adaptation of induction protocols, are also discussed. Imlifidase cleaves most of the currently used induction agents except for horse antithymocyte globulin, and rebound of donor-specific antibodies should be managed. Another consideration is the timing and interpretation of (virtual) crossmatches when bringing this novel desensitization agent into the clinic.