Journal of neurosurgery
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Journal of neurosurgery · Oct 1993
Cytotoxicity and antitumor effects of growth factor-toxin fusion proteins on human glioblastoma multiforme cells.
The prognosis of glioblastoma multiforme remains poor despite advances in treatment by surgery, irradiation, and chemotherapy. Many malignant gliomas overexpress growth factor receptors. The possibility of targeting these receptors with selective cytotoxic molecules constructed by fusing deoxyribonucleic acid (DNA)-encoding mutant forms of Pseudomonas exotoxin A (PE) with complementary DNA-encoding growth factors was investigated. ⋯ The animals were treated for 7 days via a continuous infusion pump placed in the peritoneal cavity. A constant serum level of TGF-alpha-PE40 was achieved that was nontoxic to the mice yet caused a reduction in tumor volume and retarded growth beyond the treatment period. The overexpression of the epidermal growth factor receptor in glioblastomas multiforme and the potency and specificity of the TGF-alpha-PE40 construct designed to target this receptor suggests that TGF-alpha-PE40 has the potential to be an effective antitumor agent for the adjuvant therapy of these carcinomas.