title: Targeted toxins in brain tumor therapy.
abstract: Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.
authors: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, New York 13210, NY, USA. liy@upstate.edu
authors: Yan Michael
authors: YM
authors: Li
authors: Walter A
authors: WA
authors: Hall
mesh_terms: D036002:ADP Ribose Transferases / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005098:Exotoxins / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D011994:Recombinant Proteins; D014118:Toxins, Biological / Q000008:administration & dosage / Q000627:therapeutic use*; D037521:Virulence Factors / Q000627:therapeutic use; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D004167:Diphtheria Toxin; D005098:Exotoxins; D007155:Immunologic Factors; D000922:Immunotoxins; D011994:Recombinant Proteins; D014118:Toxins, Biological; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A