Selective inhibition of growing pigment epithelial cells by a receptor-directed immunotoxin.
An immunotoxin conjugate of a murine monoclonal antibody against human transferrin receptors and the A chain of ricin was examined for its potential to inhibit selectively the growth of retinal pigment epithelial (RPE) cells which grow in an uncontrolled manner in proliferative vitreoretinopathy. The probable efficacy of such an agent in vivo stems from the observation that actively proliferating cells possess many more transferrin receptors than normal quiescent cells. The authors showed in vitro that the immunoconjugate (454A12 MAB-rRA) inhibits protein synthesis in actively dividing RPE cells but has a smaller or no effect on protein synthesis by confluent, nondividing RPE cells. The effect was specific in that neither the free ricin A chain (rRA) nor the monoclonal antibody (454A12 MAB) alone has any inhibitory effect. Furthermore, the antibody competes with the immunotoxin and suppresses the latter's toxicity. This immunotoxin has applications for therapy in conditions in which the pathologic proliferation of RPE cells occurs.
Davis
A A
AA
Department of Microbiology, University of South Carolina School of Medicine, Columbia 29208.
Whidby
D E
DE
Privette
T
T
Houston
L L
LL
Hunt
R C
RC
D000911:Antibodies, Monoclonal; D001667:Binding, Competitive / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000187:drug effects* / Q000276:immunology; D012276:Ricin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011500:Protein Synthesis Inhibitors; D011990:Receptors, Transferrin; D012276:Ricin