Effect of topically applied anti-CD4 monoclonal antibodies on orthotopic corneal allografts in a rat model.
OBJECTIVE
Monoclonal antibodies (mAb) have generated interest as therapeutic agents. Limited data are available on the treatment of corneal graft rejection. The purpose of this study was to assess the use of topically applied mAb on experimental corneal grafts.


METHODS
W 3/25, an IgG 1 mouse antirat mAb that recognizes a CD4+ cell subset, was used to treat Lewis recipient rats that received orthotopic corneal grafts of Wistar-Furth donors. Recipients were randomly assigned to receive topically applied drops of liposome-incorporated anti-CD4 mAb (LIP-anti-CD4 mAb), an equivalent amount of free anti-CD4 mAb, an isotype-matched control mAb encapsulated in liposomes (LIP-control mAb), or empty liposomes (emp-LIP) 5 times daily for 10 days. To investigate the immunologic effect of mAb treatment, flow cytometry of the targeted cells and cytotoxic activity of lymphocytes were analyzed.


RESULTS
Application of LIP-anti-CD4 mAb was effective in reducing the rejection rate (P < .05) and in prolonging the mean survival time of corneal grafts that underwent rejection (P < .05). In contrast, no significant effect on graft outcome was observed after the application of control agents. Flow cytometry analysis did not reveal systemic depletion of the targeted lymphocyte subset in any anti-CD4 mAb treated animals. Rejected grafts elicited a cellular cytotoxic immune response in a cell-mediated lymphocytotoxic assay independent of the treatment given.


CONCLUSIONS
The results suggest that treatment with topically applied LIP-anti-CD4 mAb prolongs graft survival in orthotopic corneal grafts in a rat model. The beneficial effect of LIP-anti-CD4 mAb, probably due to enhanced intraocular delivery, was achieved by using relatively low doses of mAb.
Pleyer
U
U
Jules Stein Eye Institute, UCLA School of Medicine.
Milani
J K
JK
Dukes
A
A
Chou
J
J
Lutz
S
S
Rückert
D
D
Thiel
H J
HJ
Mondino
B J
BJ
D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D006085:Graft Survival / Q000276:immunology; D015948:Keratoplasty, Penetrating / Q000276:immunology*; D008081:Liposomes; D009883:Ophthalmic Solutions; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D009883:Ophthalmic Solutions