Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors

Nat Med. 1997 Dec;3(12):1362-8. doi: 10.1038/nm1297-1362.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antibodies / blood
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Diphtheria Toxin / adverse effects
  • Diphtheria Toxin / genetics
  • Diphtheria Toxin / therapeutic use*
  • Drug Design
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Transferrin / adverse effects
  • Transferrin / genetics
  • Transferrin / therapeutic use*


  • Antibodies
  • Diphtheria Toxin
  • Transferrin