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Review
. 2022 Mar;22(3):691-697.
doi: 10.1111/ajt.16828. Epub 2021 Sep 13.

Imlifidase for the treatment of anti-HLA antibody-mediated processes in kidney transplantation

Edmund Huang  1 , Angela Q Maldonado  2 , Christian Kjellman  2 , Stanley C Jordan  1
Affiliations
Review

Imlifidase for the treatment of anti-HLA antibody-mediated processes in kidney transplantation

Edmund Huang et al. Am J Transplant. 2022 Mar.

Abstract

The IgG-degrading enzyme derived from Streptococcus pyogenes (Imlifidase, Hansa Biopharma) is a novel agent that cleaves all four human subclasses of IgG and has therapeutic potential for HLA desensitization in kidney transplantation and antibody-mediated rejection. Data from clinical trials in kidney transplantation demonstrated rapid degradation of anti-HLA donor-specific antibodies facilitating HLA-incompatible transplantation, which led to conditional approval of imlifidase by the European Medicines Agency for desensitization in kidney transplant recipients of a deceased donor with a positive cross match. Important considerations arising from the early experiences with imilfidase on kinetics of donor-specific antibodies after administration, timing of complementary therapeutic monoclonal or polyclonal IgG antibodies, and interference with cross match assays should be recognized as imlifidase emerges as a therapeutic agent for clinical transplantation.

Keywords: alloantibody; clinical research; desensitization; immune modulation; immunosuppressant - other; immunosuppression; kidney transplantation; nephrology; practice; rejection: antibody-mediated (ABMR); sensitization.

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Conflict of interest statement

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Dr. Huang has received research grants and consulting fees from CareDx, Inc. and Veloxis Pharmaceuticals and a research grant from CSL‐Behring. Drs. Maldonado and Kjellman are employees of Hansa Biopharma. Dr. Jordan has received research grants and consulting fees from CSL Behring, Amplyx, and Hansa Biopharma. He also has a patent pending for use of interleukin‐6 monoclonal antibodies for desensitization and treatment of antibody‐mediated rejection.

Figures

FIGURE 1
FIGURE 1
(A) Mechanisms of action of IdeS (IgG endopeptidase). (B) Implications of IdeS on IgG‐mediated effector functions
FIGURE 2
FIGURE 2
(A) Immune effector functions mediated by DSAs and impact on allograft injury. (B) Ides eliminates antibody‐dependent injury to allografts by degrading DSAs
See this image and copyright information in PMC

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