Long term Effect of anti-CD40 antibody treatment on the survival of corneal xenotransplantation

Abstract

Purpose : Previous study shows anti-CD154 (CD40 ligand) treatment, as an inhibitor of CD40 ligand, is effective on corneal xenotransplantation, however, anti-CD154 treatment can not be used in human clinical trial due to thromboembolism. To investigate the effect of systemically administered anti-CD40 antibodies on the survival of deep lamellar porcine corneal grafts in pig-to-rhesus corneal transplantation model.

Methods : Five Chinese rhesus macaques underwent deep lamellar corneal transplantation with clinically acceptable sized (7.5 mm in diameter) wild-type porcine corneal grafts using big bubble technique. Intravenous anti-CD40 antibodies (Abs) (30-50 mg/kg, x15/6 months) and immunoglobulin were administered as programmed schedule. Rejection sign, central corneal thickness, and recipients’ immunologic profile including memory T cells, anti-α-Gal and donor-specific Abs, and aqueous complement concentration were evaluated. Cellular infiltration into the xenografts was evaluated by immunohistochemical staining. Immunologic profiles in anti-CD40 Abs-treated groups were compared with those in in anti-CD154 Abs-treated groups in our previous report.

Results : Anti-CD 40 Abs-based immunosuppressive treatment achieved the successful survival of xenocorneal grafts (389 days, 382 days, 236 days, 201 days, >61 days) without any ocular complications. Levels of central memory or effector memory CD8+ or CD4+ T cells in anti-CD40 Abs-treated primates were not significantly different from those in anti-CD154 Abs-treated primates. Levels of donor-specific Ig G and Ig M levels, levels of anti alpha-Gal Ig G and Ig M, and non- alpha-Gal Ig G in the blood, and level of complement in aqueous humor were not increased. Histology showed that CD3+ T cells or macrophages were not found in anti-CD40 Abs-treated grafts.

Conclusions : Treatment of anti-CD40 Abs achieved long-term success on the survival of corneal deep lamellar xenotransplantation, and the effect of anti-CD40 Abs treatment appears to be comparable to the effect of Anti-CD154 Abs treatment on corneal xenotransplantation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.