Local Treatment of Brain Tumors with Targeted Chimera Cytotoxic Proteins

Abstract

High-grade astrocytomas (HGA) are the most prevalent brain tumors that represent a unique pharmaceutical challenge. Their cerebral localization and characteristic features of tumor progression primarily dictate this challenge. Targeted chimera conjugate/fusion cytotoxic proteins have become the newest class of investigative drug candidates for the treatment of HGA due to their inherent properties that are compatible with drug deliveries to brain tumors. A conjugate of a human transferrin with bacterial toxin, Diphtheria toxin, has shown clinical efficacy in Phase I and II trials when administered intratumorally through convection-enhanced delivery. This immunotoxin belongs to the first group of immunotoxins that started to live up to early expectations. Other anti-brain tumor cytotoxins have entered or will enter the clinic shortly. The clinical applicability of targeted bacterial toxin-containing cytotoxins in the treatment of brain tumors warrants further development and careful clinical evaluation.