Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107) for therapy of malignant gliomas

J Neurooncol. 2003 Oct;65(1):3-13. doi: 10.1023/a:1026246500788.


The authors review the preclinical and clinical results of the ligand-targeted toxin conjugate Transferrin-CRM107 (Tf-CRM107), for the treatment of malignant gliomas. Tf-CRM107 is a conjugate protein of diphtheria toxin with a point mutation (CRM107) linked by a thioester bond to human transferrin (Tf). This conjugate exhibits potent cytotoxicity in vitro against mammalian cells expressing the transferrin receptor with activity at picomolar concentrations. Phase I clinical trial results demonstrated that Tf-CRM107, delivered via a high-flow convection method utilizing stereotactically placed catheters, produced tumor response in patients with malignant brain tumors refractory to conventional therapy without severe neurologic or systemic toxicity. The results of a Phase II study are also summarized. Tf-CRM107 treatment results in complete and partial tumor response without severe toxicity in 35% of the evaluable patients. These data warrant a Phase III study as well as continued research in the field of targeted toxin therapy. Future directions of research include optimizing Tf-CRM107 delivery to targeted brain regions, and improving the treatment efficacy by combining with other toxin conjugates targeted to different receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacterial Toxins / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Clinical Trials as Topic
  • Drug Delivery Systems
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Transferrin / therapeutic use*


  • Bacterial Toxins
  • Tf-CRM107
  • Transferrin