Long-term inhibition of cellular proliferation by immunotoxins.

The proliferation and fibrous metaplasia of retinal glial and pigment epithelial cells cause proliferative vitreoretinopathy. The immunotoxin 454A12 MAB-rRA is composed of a murine monoclonal antibody, specific for the human transferrin receptor, and is chemically linked to recombinant ricin A chain, a cellular toxin. The rapidly proliferating cells take up the immunotoxin, but non-proliferating cells do not. Using a collagen-gel medium to simulate the vitreous, we have studied the effect of the immunotoxin on fibroblast proliferation in vitro. Exposure of the fibroblasts to 1000 ng of immunotoxin per milliliter of the collagen gel medium for 10 minutes kills 96% or more of the cells for 20 days. These in vitro data indicate that the immunotoxin is effective in an environment similar to the vitreous; however, in vivo studies will be necessary to prove if it is a suitable agent for the long-term prevention of cell proliferation in the human eye.