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[georgejjl]

Safety and efficacy of OXB-202, a Genetically-Engineered Tissue Therapy for the Prevention of Rejection In High Risk Corneal Transplant Patients.
Fouladi N1, Parker M2, Kennedy V3, Binley K4, McCloskey L5, Loader J6, Kelleher M7, Mitrophanous K8, Stout JT9, Ellis S10.
Author information
1
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
2
Oregon Health and Science University Casey Eye Institute, 14637, Portland, Oregon, United States ; [e-mail].
3
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
4
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
5
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
6
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
7
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
8
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
9
Baylor College of Medicine Department of Ophthalmology, 196293, Houston, Texas, United States ; [e-mail].
10
Oxford BioMedica (UK) Ltd, Oxford, Oxfordshire, United Kingdom of Great Britain and Northern Ireland ; [e-mail].
Abstract
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 vascularisation of the recipient cornea. The main reason for graft failure is irreversible immunological rejection and it is therefore unsurprising that neovascularisation (both pre- and post-grafting) is a significant risk factor for subsequent graft failure. Neovascularisation 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 Anaemia Virus (EIAV) called pONYK1EiA, which subsequently prevents rejection by suppressing neovascularisation. Previously we have shown that rabbit donor corneas treated with pONYK1EiA substantially suppress corneal neovascularisation, opacity and subsequent rejection in an aggressive rabbit model of cornea graft rejection2. Here we present efficacy data 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 GLP toxicology and biodistribution study of pONYK1EiA-modified rabbit corneas in a rabbit corneal transplant model. We show that pONYK1EiA-modified rabbit corneas (OXB-202) significantly reduce corneal neovascularisation 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, we have confirmed that angiogenesis is a valid target to prevent corneal graft rejection in a high-risk setting and demonstrated that 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-Man trial.

https://www.ncbi.nlm.nih.gov/pubmed/29361840

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George