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

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

  • Sci Transl Med. 2023 Aug 30;15(711):eadf6376. doi: 10.1126/scitranslmed.adf6376.
Imran J Anwar 1,  Dora M Berman 2 3,  Isabel DeLaura 1,  Qimeng Gao 1,  Melissa A Willman 2,  Allison Miller 1,  Alan Gill 4,  Cindy Gill 4,  Steve Perrin 5,  Camillo Ricordi 2 3 6 7 8,  Philip Ruiz 3,  Mingqing Song 1,  Joseph M Ladowski 1,  Allan D Kirk 1,  Norma S Kenyon 2 3 6 7
Affiliations

Affiliations

  • 1 Duke Transplant Center, Department of Surgery, Duke University School of Medicine; Durham, NC 27710, USA.
  • 2 Diabetes Research Institute, University of Miami, Miami, FL 33136, USA.
  • 3 Department of Surgery, University of Miami, Miami, FL 33136, USA.
  • 4 ALS Therapy Development Institute, Cambridge, MA 02472, USA.
  • 5 Eledon Pharmaceuticals, Irving, CA 92612, USA.
  • 6 Department of Microbiology and Immunology, University of Miami, Miami, FL 33136, USA.
  • 7 Department of Biomedical Engineering, University of Miami, Miami, FL 33136, USA.
  • 8 Department of Medicine, University of Miami, Miami, FL 33136, USA.
PMID: 37647390 DOI: 10.1126/scitranslmed.adf6376
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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