Pseudomonas exotoxin-anti-TAC. Cell-specific immunotoxin active against cells expressing the human T cell growth factor receptor.
An immunotoxin was constructed with an activity that discriminated between two T cell lines based on the expression of the T cell growth factor (TCGF) receptor on their cell surface. A toxic protein conjugate, designated PE-anti-TAC, was made by chemically coupling pseudomonas exotoxin (PE) to a monoclonal antibody (anti-TAC) that recognizes the human TCGF receptor. This conjugate was toxic to HUT-102 cells, a cell line that expresses the TCGF receptor, but was nontoxic for MOLT-4 cells, a receptor-negative line. The toxicity of PE-anti-TAC was enhanced 50-fold in the presence of human adenovirus type II and was reduced to control levels by adding excess anti-TAC antibody. The toxicity of PE-anti-TAC for HUT-102 cells was compared with PE-anti-transferrin receptor. To compare the route of entry for both anti-TAC and anti-TFR using electron microscopy, protein conjugates were made by coupling horseradish peroxidase (HRP) to each antibody. Anti-TFR-HRP entered HUT-102 cells by concentrative adsorptive endocytosis via coated pits, and the majority of the antibodies bound to the cell surface at 4 degrees C were seen in receptosomes by 10 min after warming to 37 degrees C. Anti-TAC-HRP was also found to enter HUT-102 cells via coated pits and receptosomes; but, in contrast to anti-TFR, anti-TAC did not selectively concentrate in coated pits, and therefore the majority of this surface-bound antibody were not internalized in HUT-102 cells by 10 min at 37 degrees C.
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000648:ultrastructure; D005098:Exotoxins / Q000633:toxicity*; D006735:Horseradish Peroxidase; D006801:Humans; D007938:Leukemia / Q000276:immunology; D008854:Microscopy, Electron; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D005098:Exotoxins; D006735:Horseradish Peroxidase; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A