Interleukin-2 receptor--targeted therapy by monoclonal antibodies in the rat corneal graft.
A possible selective therapeutic approach to corneal graft rejection will aim at IL-2 receptor-bearing antigen-activated T-lymphocytes with monoclonal anti IL-2R antibodies. In a rat penetrating keratoplasty model (Lewis x Lewis-BN) comparing to controls (median, 8 days), a significant delay of the allograft reaction was achieved by applying a therapeutic dose (15 mg/kg bw) of cyclosporin A (median, 18 days; p < 0.01), an intraperitoneal (1.0 mg/kg bw) (median, 13.5 days; p < 0.05) or a subconjunctival injection of IL-2R mab (0.5 mg/kg bw ART-18) (median, 16 days; p < 0.01) with low-dose Cyclosporin A (1.5 mg/kg bw). In pharmacokinetic experiments, the corneal radioactivity 24 h after intraperitoneal injection of 125I-labeled ART-18 was < 1% (p < 0.01) of the values obtained by subconjunctival injection, whereas the serum radioactivity values (p > 0.05) were in the same range. The above results suggest that the onset of an allograft reaction in perforating keratoplasty seems to depend on the locally achievable antibody concentration and can be delayed with a high level of IL-2 R mab present in the immediate surrounding of the foreign antigen-expressing cells.
Hoffmann
F
F
Department of Ophthalmology, Free University of Berlin, Germany.
Kruse
H A
HA
Meinhold
H
H
Bechrakis
N E
NE
Heimann
H
H
Diamanstein
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection / Q000628:therapy*; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D015948:Keratoplasty, Penetrating; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D016572:Cyclosporine