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Am J Transplant. 2018 Sep;18(9):2330-2341. doi: 10.1111/ajt.14913. Epub 2018 Jun 1.

Comparative efficacy of anti-CD40 antibody-mediated costimulation blockade on long-term survival of full-thickness porcine corneal grafts in nonhuman primates.

Author information

1
Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.
2
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
3
Translational Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.
4
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Gyeonggi-do, Korea.
5
Department of Microbiology and Immunology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

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.

KEYWORDS:

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

PMID:
29722120
DOI:
10.1111/ajt.14913

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