Use of Monoclonal Antibodies in Corneal Transplantation

Murine monoclonal antibodies are used to abrogate immunological rejection of vascularised organ grafts in humans. The most widely-used antibody, muromonab CD3 (OKT3), has specificity for the human peripheral T cell antigen CD3. Systemic administration of muromonab CD3 in essential organ transplantation is associated with 2 major types of complications: infections and the so-called cytokine release syndrome. In addition, most recipients produce antibodies to the heterologous murine immunoglobulin. Muromonab CD3 has also been implicated in precipitating some ocular complications. Some of these adverse effects are likely to be attendant on the administration of any immunosuppressive murine monoclonal antibody, irrespective of specificity. The use of monoclonal antibodies in corneal transplantation has thus far been limited, and has been restricted primarily to studies in experimental animals. Systemic administration of monoclonal antibodies with specificity for the T cell subset determinant CD4 has already been shown to prolong orthotopic corneal allograft and heterotopic corneal xenograft survival in small rodents. Further, the intracameral injection of anti-T cell monoclonal antibodies into the anterior chamber of the eye has been shown to reverse acute corneal graft rejection in humans, while antibodies with specificity for T cells and myeloid cells were similarly effective in a rabbit model. These studies clearly demonstrate that monoclonal antibodies can be used to both prevent and reverse corneal graft rejection. The challenges are now 3-fold. First, the most appropriate specificity and route of administration of monoclonal antibodies for the immunosuppression of corneal grafts need to be determined. Secondly, it will be necessary to establish that these reagents can be given safely in the clinical setting without causing unacceptable adverse effects. Finally, it must be confirmed that monoclonal antibodies will prove to be useful adjuncts (or better alternatives) to existing regimens of immunosuppression for corneal transplantation.