In vivo T-cell ablation by a holo-immunotoxin directed at human CD3.
We have evaluated the in vivo efficacy of anti-CD3-CRM9, a holo-immunotoxin constructed with a diphtheria toxin binding-site mutant. Eighty percent of established human T-cell subcutaneous tumors in nude mice completely regressed following intraperitoneal injection of immunotoxin at a dose set at half the minimum lethal dose assayed in toxin-sensitive animals. Similar regressions produced by a 137Cs source required a dose in excess of 500 cGy. The high degree of in vivo T-cell ablation produced by this immunotoxin is apparently due to maintenance of the toxin translocation function provided by CRM9 and a necessary intracellular routing function supplied by CD3. This immunotoxin may be useful in treating conditions caused by pathologic oligoclonal T-cell expansion such as graft-versus-host disease, autoimmune diseases, and possibly AIDS.
Section on Biophysical Chemistry, National Institute of Mental Health, Bethesda, MD 20892.
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DM
Neville
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Scharff
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Srinivasachar
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D018956:CD5 Antigens; D004167:Diphtheria Toxin / Q000008:administration & dosage; D007167:Immunotherapy; D000922:Immunotoxins / Q000633:toxicity*; D015458:Leukemia, T-Cell / Q000628:therapy; D008212:Lymphocyte Depletion; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018956:CD5 Antigens; D004167:Diphtheria Toxin; D000922:Immunotoxins; D011948:Receptors, Antigen, T-Cell