June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Comparative efficacy of anti-CD40 antibody mediated-costimulation blockade and anti-CD20 antibody/tacrolimus treatment on the survival of full thickness xenocorneal transplantation in non-human primates
Author Affiliations & Notes
  • Mee Kum Kim
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Chang Ho Yoon
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Jaeyoung Kim
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Hyun Ju Lee
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hyunsang Kwon
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Hee Jung Kang
    Department of Laboratory Medicine , Hallym University College of Medicine, Seoul, Korea (the Republic of)
  • Chung-Gyu Park
    Department of Microbiology and Immunology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Eung-Soo Hwang
    Department of Microbiology and Immunology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Won Ryang Wee
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
    Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Mee Kum Kim, None; Chang Ho Yoon, None; Jaeyoung Kim, None; Hyun Ju Lee, None; Hyunsang Kwon, None; Hee Jung Kang, None; Chung-Gyu Park, None; Eung-Soo Hwang, None; Won Ryang Wee, None
  • Footnotes
    Support  This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (Project No. HI13C0954). Anti-CD40 Ab used in this study were provided by the Nonhuman Primate Reagent Resource supported by U.S. National Institutes of Health NIAID contract HHSN272201300031C and grant OD010976.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 974. doi:
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      Mee Kum Kim, Chang Ho Yoon, Jaeyoung Kim, Hyun Ju Lee, Hyunsang Kwon, Hee Jung Kang, Chung-Gyu Park, Eung-Soo Hwang, Won Ryang Wee; Comparative efficacy of anti-CD40 antibody mediated-costimulation blockade and anti-CD20 antibody/tacrolimus treatment on the survival of full thickness xenocorneal transplantation in non-human primates. Invest. Ophthalmol. Vis. Sci. 2017;58(8):974.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To analyze comparative efficacy and safety of systemically administered anti- CD40 antibody or anti-CD20 antibody/tacrolimus on the survival of full-thickness porcine corneal grafts in pig-to-rhesus corneal transplantation model.

Methods : Twelve Chinese rhesus macaques were assigned to anti-CD40 (2C10R4) or anti-CD20 (Rituximab) treated group and underwent full thickness corneal transplantation with clinically acceptable sized (7.5 mm in diameter) porcine grafts using wild-type SNU miniature pigs. Intravenous anti-CD40 or anti-CD20 antibody/tacrolimus and immunoglobulin were administered as programmed schedule. Graft survival was 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 humor were evaluated.

Results : Anti-CD 40 antibody-based immunosuppressive treatment achieved 83.3% of 6 months-the survival of xenocorneal grafts (>384 , >307 , >273 , >203 , >196 , 41days), and anti-CD20 antibody-based treatment achieved similar survival (>260, >251, >251, 134, >102, >97 days), which was statistically insignificant (p=0.9064, Log Rank test). Rejected primates (n=2) showed the increase of CD8+ effector memory T cells around the rejection time. Levels of donor-specific IgG and IgM, anti αGal IgG and IgM and complement were not increased in all primates except rejected ones. No Porcine endogenous retrovirus or Cytomegalovirus were detected in all treated primates. While general conditions, liver function and renal function test were within normal ranges in all anti-CD40 antibody treated primates, anti-CD 20 antibody treated primates developed shigellosis, pneumonitis, and severe decrease of the platelet which was recovered after discontinuation of immune suppressants.

Conclusions : The effect of anti-CD40 antibody treatment is effective and safe on the survival of full thickness corneal xenotransplantation in primates, while the anti-CD20 antibody treatment is comparably effective on the survival but develops more systemic complications than anti-CD40 antibody regimen.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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