Inhibition of human subconjunctival fibroblast proliferation by immunotoxin.
The ability to target proliferating cells is important for agents used to modulate wound healing by decreasing the growth of fibroblasts. Proliferating cells are known to express increased numbers of transferrin receptors and have increased receptor turnover. 454A12 Mab-rRA, an immunotoxin containing anti-human transferrin receptor monoclonal antibody conjugated to recombinant ricin A chain, was shown to inhibit the proliferation of human subconjunctival fibroblasts in vitro. A dose-related reduction of cell counts was observed in proliferating cells. More than 90% inhibition was achieved with an immunotoxin concentration of 10 ng/ml per 20,000 cells plated. In contrast, confluent fibroblasts were markedly less sensitive to the immunotoxin at equivalent concentrations. Comparative experiments demonstrated that 5-fluorouracil has less specificity for proliferating cells, with significant death of confluent fibroblasts at high drug concentrations.
Wilkerson
M
M
Duke University Eye Center, Durham, North Carolina.
Fulcher
S
S
Shields
M B
MB
Foulks
G N
GN
Hatchell
D L
DL
Houston
L L
LL
D000911:Antibodies, Monoclonal; D002452:Cell Count; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005472:Fluorouracil / Q000494:pharmacology; D005901:Glaucoma / Q000601:surgery; D006801:Humans; D000922:Immunotoxins / Q000502:physiology*; D008858:Microscopy, Phase-Contrast; D011990:Receptors, Transferrin; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D005472:Fluorouracil