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

Abstract

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.

• Authors: Michael Weaver, Douglas W Laske
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 65 Issue 1 Pg. 3-13 (Oct 2003) ISSN: 0167-594X [Print] United States
• PMID: 14649881 (Publication Type: Journal Article, Review)

Chemical References

• Bacterial Toxins
• Tf-CRM107
• Transferrin

Topics

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