Generation of active immunotoxins containing recombinant restrictocin.
Restrictocin, a toxin produced by the fungus Aspergillus restrictus, is a potent inhibitor of eukaryotic protein synthesis. Recombinant restrictocin was made in Escherichia coli and purified to homogeneity in large amounts. The recombinant protein was found to be poorly immunogenic in mice with low toxicity, when injected intraperitoneally. Two immunotoxins were constructed by coupling the recombinant restrictocin to an antibody to the human transferrin receptor, using a cleavable and a stable linkage. The immunotoxins so generated showed specific cytotoxic activity toward receptor bearing cells in tissue culture. Immunotoxin with a cleavable linkage, however, was more active than that containing a stable linkage. Restrictocin appears to be a promising candidate to be developed as a chimeric toxin for targeted therapy.
Rathore
D
D
Immunochemistry Laboratory, National Institute of Immunology, New Delhi, India.
Batra
J K
JK
D000485:Allergens; D000818:Animals; D052179:Antigens, Plant; D005656:Fungal Proteins / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D011500:Protein Synthesis Inhibitors / Q000737:chemistry*; D011990:Receptors, Transferrin / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins; D012260:Ribonucleases / Q000737:chemistry* / Q000276:immunology; D014407:Tumor Cells, Cultured
C081947:ASPF1 protein, Aspergillus fumigatus; D000485:Allergens; D052179:Antigens, Plant; D005656:Fungal Proteins; D000922:Immunotoxins; D011500:Protein Synthesis Inhibitors; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C036196:MITF protein, Aspergillus restrictus; D012260:Ribonucleases