Journal of Neuro-Oncology

, Volume 65, Issue 1, pp 3–14

Transferrin Receptor Ligand-Targeted Toxin Conjugate (Tf-CRM107) for Therapy of Malignant Gliomas

  • Michael Weaver
  • Douglas W. Laske

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.

convection enhanced delivery diphtheria toxin glioblastoma multiforme (GBM) malignant brain tumor targeted toxin transferrin transferrin receptor 

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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Michael Weaver
    • 1
  • Douglas W. Laske
    • 1
  1. 1.Department of NeurosurgeryTemple University School of MedicinePhiladelphiaUSA

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