Antisense VEGF Tumor Gene Therapy for Malignant Gliomas (Anti-angiogenic Gene Therapy)

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With increasing size tumors are continually dependent on functional blood vessel system to guarantee the supply with oxygen and nutrients. VEGF is a key mediator not only of developmental but also of hypoxia-mediated and tumor-induced angiogenesis. Gene therapy using antisense VEGF with the aim to inhibit tumor angiogenesis may be a successful strategy for the treatment of highly vascular and invasive malignant gliomas. We investigated whether the blockage of VEGF/VEGFR paracrine loop may inhibit the tumor-angiogenesis. Several strategies, such as antisense VEGF, endothelial progenitor cells, HIF-1 decoy, siRNA, were adopted to block this pathway. Antisense VEGF introduced by retrovirus vectors showed a significant inhibition of VEGF expression, angiogenesis, tumor growth and prolongation of survival time without any serious adverse effects. Therefore, our study supports the concept that anti-angiogenic tumor therapy is a promising therapy for malignant gliomas.