title: Diphtheria toxin-based targeted toxin therapy for brain tumors.
abstract: Targeted toxins (TT) are molecules that bind cell surface antigens or receptors such as the transferrin or interleukin-13 receptor that are overexpressed in cancer. After internalization, the toxin component kills the cell. These recombinant proteins consist of an antibody or carrier ligand coupled to a modified plant or bacterial toxin such as diphtheria toxin (DT). These fusion proteins are very effective against brain cancer cells that are resistant to radiation therapy and chemotherapy. TT have shown an acceptable profile for toxicity and safety in animal studies and early clinical trials have demonstrated a therapeutic response. This review summarizes the characteristics of DT-based TT, the animal studies in malignant brain tumors and early clinical trial results. Obstacles to the successful treatment of brain tumors include poor penetration into tumor, the immune response to DT and cancer heterogeneity.
authors.affiliation: Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY 13210, USA. liy@upstate.edu
authors.forename: Yan Michael
authors.initials: YM
authors.lastname: Li
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Vallera
authors.forename: Walter A
authors.initials: WA
authors.lastname: Hall
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D014168:Transferrin / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001427:Bacterial Toxins; C512526:DTAT13 protein; D004167:Diphtheria Toxin; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; C404391:Tf-CRM107; D014168:Transferrin; C471586:diphtheria toxin-urokinase fusion protein, human