Safety and Efficacy of OXB-202, a Genetically Engineered Tissue Therapy for the Prevention of Rejection in High-Risk Corneal Transplant Patients

Hum Gene Ther. 2018 Jun;29(6):687-698. doi: 10.1089/hum.2017.184. Epub 2018 Mar 19.


Due to both the avascularity of the cornea and the relatively immune-privileged status of the eye, corneal transplantation is one of the most successful clinical transplant procedures. However, in high-risk patients, which account for >20% of the 180,000 transplants carried out worldwide each year, the rejection rate is high due to vascularization of the recipient cornea. The main reason for graft failure is irreversible immunological rejection, and it is therefore unsurprising that neovascularization (NV; both pre and post grafting) is a significant risk factor for subsequent graft failure. NV is thus an attractive target to prevent corneal graft rejection. OXB-202 (previously known as EncorStat®) is a donor cornea modified prior to transplant by ex vivo genetic modification with genes encoding secretable forms of the angiostatic human proteins, endostatin and angiostatin. This is achieved using a lentiviral vector derived from the equine infectious anemia virus called pONYK1EiA, which subsequently prevents rejection by suppressing NV. Previously, it has been shown that rabbit donor corneas treated with pONYK1EiA substantially suppress corneal NV, opacity, and subsequent rejection in an aggressive rabbit model of cornea graft rejection. Here, efficacy data are presented in a second rabbit model, which more closely mirrors the clinical setting for high-risk corneal transplant patients, and safety data from a 3-month good laboratory practice toxicology and biodistribution study of pONYK1EiA-modified rabbit corneas in a rabbit corneal transplant model. It is shown that pONYK1EiA-modified rabbit corneas (OXB-202) significantly reduce corneal NV and the rate of corneal rejection in a dose-dependent fashion, and are tolerated with no adverse toxicological findings or significant biodistribution up to 13 weeks post surgery in these rabbit studies. In conclusion, angiogenesis is a valid target to prevent corneal graft rejection in a high-risk setting, and transplanted genetically modified corneas are safe and well-tolerated in an animal model. These data support the evaluation of OXB-202 in a first-in-human trial.

Keywords: corneal rejection; gene therapy; genetic modification; keratoplasty; transplant; viral vectors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiostatins / metabolism
  • Animals
  • Cell Count
  • Cell- and Tissue-Based Therapy*
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / therapy
  • Corneal Opacity
  • Corneal Transplantation / adverse effects*
  • Culture Media
  • Endostatins / metabolism
  • Endothelial Cells / pathology
  • Female
  • Genetic Engineering*
  • Genetic Vectors / metabolism
  • Graft Rejection / pathology
  • Graft Rejection / physiopathology
  • Graft Rejection / prevention & control*
  • HEK293 Cells
  • Humans
  • Intraocular Pressure
  • Keratoplasty, Penetrating
  • Rabbits
  • Risk Factors
  • Tissue Distribution


  • Culture Media
  • Endostatins
  • Angiostatins