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

• DOI: 10.1126/scitranslmed.adf6376
• Publication Date: 2023-08-30T17:59:22Z
• Authors: Imran J. Anwar; Dora M. Berman; Isabel DeLaura; Qimeng Gao; Melissa A. Willman; Allison Miller; Alan Gill; Cindy Gill; Steve Perrin; Camillo Ricordi; Philip Ruiz; Mingqing Song; Joseph M. Ladowski; Allan D. Kirk; Norma S. Kenyon
• Keywords: Macaca fascicularis; CD40 Ligand; Animals; Antibodies, Monoclonal; Ligands; Kidney; Allografts; Macaca mulatta; 3. Good health

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.