Targeting CD38 in Antibody-Mediated Rejection
Antibody-mediated rejection (AMR) remains a major challenge in clinical transplantation. Current therapies have yielded inconsistent outcomes, highlighting the need for innovative approaches. CD38, a multifunctional glycoprotein, is highly expressed on plasma cells and natural killer (NK) cells, pot...
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Frontiers Media S.A.
2025-05-01
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| Series: | Transplant International |
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| Online Access: | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14343/full |
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| author | Katharina A. Mayer Klemens Budde Matthias Diebold Matthias Diebold Philip F. Halloran Georg A. Böhmig |
| author_facet | Katharina A. Mayer Klemens Budde Matthias Diebold Matthias Diebold Philip F. Halloran Georg A. Böhmig |
| author_sort | Katharina A. Mayer |
| collection | DOAJ |
| description | Antibody-mediated rejection (AMR) remains a major challenge in clinical transplantation. Current therapies have yielded inconsistent outcomes, highlighting the need for innovative approaches. CD38, a multifunctional glycoprotein, is highly expressed on plasma cells and natural killer (NK) cells, potentially offering a dual mechanism of action that could intervene in the pathophysiologic course of AMR: depleting alloantibody-producing plasma cells and NK cells. This review focuses on recent results from CD38-targeted therapies, with felzartamab emerging as a promising option. Previous case reports and series suggested that off-label daratumumab treatment could effectively reverse AMR. Felzartamab has now demonstrated safety and efficacy in a phase 2 trial for late AMR. Reductions in microvascular inflammation, downregulation of rejection-associated transcripts, and decreases in donor-derived cell-free DNA paralleled a substantial decrease in NK cell counts. However, felzartamab did not significantly affect donor-specific antibodies, which may reflect its distinct mechanism of action, primarily involving antibody-dependent cellular cytotoxicity and phagocytosis. The effects on rejection activity may have a rapid onset, but are transient. The potential benefits of prolonged therapy are currently being investigated in a recently launched phase III trial. Future studies may expand the applications of CD38 targeting to early AMR or broader indications, such as DSA-negative microvascular inflammation. |
| format | Article |
| id | doaj-art-13e091aa21d04084a3e41cfaaf1e4ea6 |
| institution | DOAJ |
| issn | 1432-2277 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Transplant International |
| spelling | doaj-art-13e091aa21d04084a3e41cfaaf1e4ea62025-08-20T03:09:57ZengFrontiers Media S.A.Transplant International1432-22772025-05-013810.3389/ti.2025.1434314343Targeting CD38 in Antibody-Mediated RejectionKatharina A. Mayer0Klemens Budde1Matthias Diebold2Matthias Diebold3Philip F. Halloran4Georg A. Böhmig5Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDepartment of Nephrology, Charité Universitätsmedizin Berlin, Berlin, GermanyDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaClinic for Transplantation Immunology and Nephrology, University Hospital Basel, University of Basel, Basel, SwitzerlandAlberta Transplant Applied Genomics Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, CanadaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaAntibody-mediated rejection (AMR) remains a major challenge in clinical transplantation. Current therapies have yielded inconsistent outcomes, highlighting the need for innovative approaches. CD38, a multifunctional glycoprotein, is highly expressed on plasma cells and natural killer (NK) cells, potentially offering a dual mechanism of action that could intervene in the pathophysiologic course of AMR: depleting alloantibody-producing plasma cells and NK cells. This review focuses on recent results from CD38-targeted therapies, with felzartamab emerging as a promising option. Previous case reports and series suggested that off-label daratumumab treatment could effectively reverse AMR. Felzartamab has now demonstrated safety and efficacy in a phase 2 trial for late AMR. Reductions in microvascular inflammation, downregulation of rejection-associated transcripts, and decreases in donor-derived cell-free DNA paralleled a substantial decrease in NK cell counts. However, felzartamab did not significantly affect donor-specific antibodies, which may reflect its distinct mechanism of action, primarily involving antibody-dependent cellular cytotoxicity and phagocytosis. The effects on rejection activity may have a rapid onset, but are transient. The potential benefits of prolonged therapy are currently being investigated in a recently launched phase III trial. Future studies may expand the applications of CD38 targeting to early AMR or broader indications, such as DSA-negative microvascular inflammation.https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14343/fullantibody-mediated rejectionCD38natural killer cellskidney transplantationtreatment |
| spellingShingle | Katharina A. Mayer Klemens Budde Matthias Diebold Matthias Diebold Philip F. Halloran Georg A. Böhmig Targeting CD38 in Antibody-Mediated Rejection Transplant International antibody-mediated rejection CD38 natural killer cells kidney transplantation treatment |
| title | Targeting CD38 in Antibody-Mediated Rejection |
| title_full | Targeting CD38 in Antibody-Mediated Rejection |
| title_fullStr | Targeting CD38 in Antibody-Mediated Rejection |
| title_full_unstemmed | Targeting CD38 in Antibody-Mediated Rejection |
| title_short | Targeting CD38 in Antibody-Mediated Rejection |
| title_sort | targeting cd38 in antibody mediated rejection |
| topic | antibody-mediated rejection CD38 natural killer cells kidney transplantation treatment |
| url | https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14343/full |
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