Comparative efficacy of anti‐CD40 antibody–mediated costimulation blockade on long‐term survival of full‐thickness porcine corneal grafts in nonhuman primates. Issue 9 (1st June 2018)

• Record Type: Journal Article
• Authors: Kim, Jaeyoung; Choi, Se Hyun; Lee, Hyun Ju; Kim, Hong Pyo; Kang, Hee Jung; Kim, Jong Min; Hwang, Eung Soo; Park, Chung‐Gyu; Kim, Mee Kum
• Is Part Of: American journal of transplantation. Volume 18:Issue 9(2018)
• Page Start: 2330
• Page End: 2341
• Publication Date: 2018-06-01
• Subjects: animal models: nonhuman primate -- animal models: porcine -- clinical research/practice -- corneal transplantation/ophthalmology -- graft survival -- immunosuppressant ‐ fusion proteins and monoclonal antibodies: B cell specific -- immunosuppressant ‐ fusion proteins and monoclonal antibodies: costimulation molecule specific -- xenotransplantation; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14913
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Porcine corneas may be good substitutes for human corneas in donor shortage. Therefore, we evaluated the efficacy and safety of an anti‐CD40 antibody–based regimen compared with an anti‐CD20 antibody–based regimen on the survival of full‐thickness corneas in pig‐to‐rhesus xenotransplant. Thirteen Chinese rhesuses underwent full‐thickness corneal xenotransplant. Six were administered anti‐CD40 antibody, and the others were administered anti‐CD20 antibody, basiliximab, and tacrolimus. Graft survival and changes in lymphocyte, donor‐specific and anti–Galα1, 3Galβ1, 4GlcNAc‐R (αGal) antibody, and aqueous complement levels were evaluated. Treatment with the anti‐CD40 antibody (>511, >422, >273, >203, >196, 41 days) and anti‐CD20 antibody (>470, 297, >260, >210, >184, 134, >97 days) resulted in long‐term survival of grafts. In the anti‐CD20 group, the number of activated B cells was significantly lower than that in the anti‐CD40 group, and the level of aqueous complements at 6 months was significantly higher than the preoperative level. There were no differences in the levels of T cells or donor‐specific and anti‐αGal antibodies between the 2 groups. In the anti‐CD20 group, 3 primates had adverse reactions. In conclusion, both the anti‐CD40 antibody– and the anti‐CD20 antibody–based protocols were effective for the long‐term survival of full‐thickness corneal xenografts, but the anti‐CD40 antibody–based treatment had fewer adverse effects. Abstract : This study suggests that both anti‐CD40 and anti‐CD20 antibody‐mediated regimens are effective for the long‐term survival of grafts in full‐thickness pig‐to‐nonhuman primate corneal xenotransplantation.