Verotoxin induces apoptosis and the complete, rapid, long-term eliminationof human astrocytoma xenografts in nude mice

Verotoxin 1 (VT1) is an E. coli elaborated subunit toxin active only agains t (tumor) cell lines that express the VT1 receptor, globotriaosyl ceramide- Gb(3). Astrocytomas can be highly malignant brain tumors that remain refrac tory to clinical treatment. Some human astrocytoma cell lines are particula rly sensitive to VT1 in vitro. To address whether this represents a feasibl e approach to the elimination of these tumors in man, human astrocytoma tum or xenografts in nude mice were treated with verotoxin. Following a single low-dose intratumoral injection of VT1, complete regression of a 1-cm-diame ter tumor within 10 days was observed in all treated animals, without reocc urrence (up to 60 days). Apoptosis was demonstrated in both tumor and vascu lar cells within the treated xenograft. Verotoxin binding to tumor cells an d blood vessels in sections of primary glioblastoma multiforme was found.