Angiogenesis appears to be a fundamental requirement for tumor growth, invasion and metastasis. Evidence also exists to suggest that inhibition of tumor-associated angiogenesis can retard tumor growth and prevent tumor spread. Several naturally occurring angiogenesis inhibitors have been identified, including type I interferons (alpha/beta). These proteins are potent inhibitors of angiogenesis and may also have direct anti-tumor and immunomodulatory effects. Because anti-angiogenic therapy is likely cytostatic, long-term delivery of angiogenesis inhibitors may be required for the successful treatment of cancer. We have, therefore, explored the utility of a gene therapy-mediated approach for the delivery of interferon-beta and tested this approach, both alone and in combination with conventional chemotherapy, in murine models of neuroblastoma.