title: Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors.
abstract: We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1-4 weeks after treatment in three of three patients at 1.0 microg/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. Direct interstitial infusion can be used successfully to distribute a large protein in the tumor and infiltrated brain surrounding the tumor.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Laske
authors.forename: R J
authors.initials: RJ
authors.lastname: Youle
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D015195:Drug Design; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D014168:Transferrin / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D004167:Diphtheria Toxin; D014168:Transferrin