Posters

Anti-CD40 antibody-mediated costimulation blockade promotes survival of full thickness porcine corneal grafts in non-human primates

Poster Details

First Author: J. Kim KOREA, SOUTH

Co Author(s):    H. Lee   S. Han   H. Kang   J. Kim   W. Wee   M. Kim     

Abstract Details

Purpose:

Previous study shows anti-CD154 (CD40 ligand) antibody-mediated costimulatory blockade is effective on corneal xenotransplantation. However, anti-CD154 antibody cannot be used for human clinical trial due to thromboembolism. Therefore, we investigated the efficacy of anti-CD40 antibody-mediated costimulatory blockade on the survival of full-thickness porcine corneal grafts in non-human primates.

Setting:

Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea.

Methods:

Six Chinese rhesus macaques underwent penetrating keratoplasty with clinically acceptable sized (7.5 to 8.0mm in diameter) wild-type porcine corneal grafts from SNU miniature pigs. Intravenous anti-CD40 antibodies were administered as programmed schedules. Graft survival, central corneal thickness, and intraocular pressure were evaluated. Changes in effector and memory T and B cell subsets, anti αGal and donor-specific antibodies were investigated in the blood, and the changes in complement levels in aqueous and blood were evaluated. Immunologic profiles in anti-CD40 antibody-treated group were compared with those in anti-CD154 antibody-treated group in our previous report.

Results:

Anti-CD40 mediated immunosuppression achieved the successful survival of xenocorneal grafts in 5 primates (>203, >196, >133, >56, >56 days) so far. One primate suffered rejection at 41 days. Levels of central or effector memory CD8+ or CD4+ T cells in all primates were not significantly different from those in anti-CD154 antibody-treated primates. Levels of donor-specific IgG and IgM, anti αGal IgG and IgM and complement were not increased in all primates except a rejected one. Histology showed a few CD3 T cells were infiltrated in a graft-host junction, however no cells were observed in the grafts.

Conclusions:

Anti-CD40 antibody mediated costimulatory blockade seems to be comparably effective on the survival of full-thickenss xenocorneal transplantation.

Financial Disclosure:

NONE