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The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.

Author information

Affiliations

  • 1. Duke Transplant Center, Department of Surgery, Duke University School of Medicine; Durham, NC 27710, USA.
      Authors
    • Anwar IJ 1
    • DeLaura I 1
    • Gao Q 1
    • Miller A 1
    • Song M 1
    • Ladowski JM 1
    • Kirk AD 1
    (7 authors)
  • 2. Diabetes Research Institute, University of Miami, Miami, FL 33136, USA.
      Authors
    • Berman DM 2, 5
    • Willman MA 2
    • Ricordi C 2, 5
    • Kenyon NS 2, 5
    (4 authors)
  • 3. ALS Therapy Development Institute, Cambridge, MA 02472, USA.
      Authors
    • Gill A 3
    • Gill C 3
    (2 authors)
  • 4. Eledon Pharmaceuticals, Irving, CA 92612, USA.
      Authors
    • Perrin S 4
    (1 author)
  • 5. Department of Surgery, University of Miami, Miami, FL 33136, USA.
      Authors
    • Berman DM 2, 5
    • Ricordi C 2, 5
    • Ruiz P 5
    • Kenyon NS 2, 5
    (4 authors)

ORCIDs linked to this article

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Science Translational Medicine, 30 Aug 2023, 15(711):eadf6376
https://doi.org/10.1126/scitranslmed.adf6376 PMID: 37647390 

Abstract 

Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation. AT-1501 monotherapy led to long-term graft survival in both islet and kidney transplant models, confirming its immunosuppressive potential. Furthermore, AT-1501-based regimens after islet transplant resulted in higher C-peptide, greater appetite leading to weight gain, and reduced occurrence of cytomegalovirus reactivation compared with conventional immunosuppression. These data support AT-1501 as a safe and effective agent to promote both islet and kidney allograft survival and function in nonhuman primate models, warranting further testing in clinical trials.

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Read article at publisher's site: https://doi.org/10.1126/scitranslmed.adf6376

Read article for free, from open access legal sources, via Unpaywall: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10990482Unpaywall

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