Novel therapies for treatment of antibody-mediated rejection of the kidney.

PURPOSE OF REVIEW

We aim to discuss current literature on novel therapies for antibody-mediated rejection (AMR) in kidney transplantation with a focus on chronic AMR.

RECENT FINDINGS

IL-6/IL-6 receptor blockers appear promising in the treatment of chronic AMR. Blocking this pathway was shown to reduce human leucocyte antigen-antibodies, improve histologic inflammation and increase T-regulatory cells. Based on experience in desensitization, IgG degrading endopeptidase, imlifidase, could be effective in AMR. There have been case reports describing the successful use of plasma cell/natural killer-cell-directed anti-CD38 antibody in the treatment of AMR. Off-target effects have been noted and strategies to mitigate these will be needed when using these agents. Complement inhibitors could be an effective add-on strategy to antibody-depleting therapies but their role in AMR needs to be better defined. Combining proteasome inhibitors and costimulation blockers has shown encouraging results in the prevention of AMR in animal models and is now being investigated in humans. Other novel strategies such as Fc neonatal receptor blockers which inhibit the recycling of pathogenic IgG and bispecific antibodies against B-cell maturation antigen/CD3+ T cells warrant further investigation.

SUMMARY

There are now a number of emerging therapies with varied targets and mechanism(s) of action that hold promise in the management of AMR and improving allograft survival.