Targeted toxins as anticancer agents.
Transformed cells, such as those found in breast cancer, often overexpress a variety of cell surface receptors and antigens. Antibodies or growth factors that specifically recognize these membrane-bound structures can be linked with protein toxins, resulting in cell-specific cytotoxic reagents. Many of these cytotoxic molecules have been produced and are referred to as oncotoxins, mitotoxins, or immunotoxins, depending on the components of the chimeric molecule. These bifunctional reagents are constructed as either chemical conjugates or fusion proteins between a ligand/antibody and a toxin. This report focuses on the use of cytotoxic proteins targeted to epidermal growth factor receptors, fibroblast growth factor receptors, erbB-2/HER-2, and tumor-associated carbohydrate antigens. Using immunotoxin therapy, total regression of established tumors in animal xenograft models have been demonstrated. These results suggest that immunotoxin molecules offer exciting opportunities for the treatment of human cancer.
Siegall
C B
CB
Department of Molecular Immunology, Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington 98121.
D000818:Animals; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins / Q000008:administration & dosage; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy; D018739:Oncogene Proteins v-erbB; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D000922:Immunotoxins; D018739:Oncogene Proteins v-erbB; D017468:Receptors, Fibroblast Growth Factor; D015682:Retroviridae Proteins, Oncogenic; D066246:ErbB Receptors