Clinical Trials with Intracerebral Convection-Enhanced Delivery of Targeted Toxins in Malignant Glioma

N.   G.   Rainov; K.      Gorbatyuk; V.      Heidecke

Abstract

Currently used targeted toxins are recombinant molecules specifically binding to surface receptors overexpressed on tumor cells. These recombinant proteins consist of a tumor-selective ligand coupled to a truncated peptide toxin. Ligands may bind to tumor-associated molecules with receptor signaling properties, such as epidermal growth factor receptor, transferrin receptor, and interleukin-13 or interleukin-4 receptors. The toxin part of the molecule in all clinically used toxins is a modified bacterial polypeptide fused to one of the above ligands. Targeted toxins are very effective against tumor cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated some evidence for tumor response. Currently, phase 3 trials with some targeted toxins are underway and final results are still pending. This review summarizes the study protocols and key findings of the most important clinical studies with targeted toxins in malignant glioma patients. It offers in addition an outlook into future areas of development of targeted toxins, such as improved delivery modes and non-invasive imaging of toxin distribution.

Keywords: Convection-enhanced delivery, glioblastoma, glioma, targeted toxin

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