Comparative efficacy of anti‐ CD CD 40 antibody–mediated costimulation blockade on long‐term survival of full‐thickness porcine corneal grafts in nonhuman primates

摘要

Porcine corneas may be good substitutes for human corneas in donor shortage. Therefore, we evaluated the efficacy and safety of an anti‐ CD 40 antibody–based regimen compared with an anti‐ CD 20 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‐ CD 40 antibody, and the others were administered anti‐ CD 20 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‐ CD 40 antibody (511, 422, 273, 203, 196, 41?days) and anti‐ CD 20 antibody (470, 297, 260, 210, 184, 134, 97?days) resulted in long‐term survival of grafts. In the anti‐ CD 20 group, the number of activated B cells was significantly lower than that in the anti‐ CD 40 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‐ CD 20 group, 3 primates had adverse reactions. In conclusion, both the anti‐ CD 40 antibody– and the anti‐ CD 20 antibody–based protocols were effective for the long‐term survival of full‐thickness corneal xenografts, but the anti‐ CD 40 antibody–based treatment had fewer adverse effects.