Evaluation of monoclonal antibodies for the development of breast cancer immunotoxins.
Eighty-five antibodies recognizing breast cancer-selective antigens were conjugated to ricin toxin A-chain using a disulfide linkage. The cytotoxicities of the resulting immunotoxins were determined on breast cancer cells and normal human fibroblasts. Twenty-four antibodies formed immunotoxins that were toxic to at least one breast cancer cell line at concentrations of 10 nM or less but were nontoxic to human fibroblast lines used as negative controls. Some of the breast tumor-selective immunotoxins were as toxic as a conjugate between monoclonal anti-transferrin receptor and ricin toxin A-chain (50% inhibition of cellular protein synthesis at approximately 0.1 nM). Another set of four immunotoxins were indiscriminately toxic to human breast tumor cell lines, two human fibroblast cell lines, and a human lymphoblastoid line. Several of the antibodies the toxin conjugates of which specifically killed breast cancer cell lines may be useful in cancer therapy, since they show a wide range of binding to individual breast tumors and cell lines and a limited range of binding to normal tissue types.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003603:Cytotoxins / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008715:Methionine / Q000378:metabolism; D012276:Ricin / Q000008:administration & dosage* / Q000627:therapeutic use; D013462:Sulfur Radioisotopes; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D003603:Cytotoxins; D013462:Sulfur Radioisotopes; D012276:Ricin; D008715:Methionine