585. Anti-Angiogenic Drugs Synergize with a Membrane Macrophage Colony Stimulating Factor (mM-CSF) Based Tumor Vaccine to Therapeutically Treat Rats with an Established Intracranial Glioma

Glioblastoma multiforme (GBM) are lethal brain tumors in humans with survival times of less than a year. We report that we successfully treated >90% of the rats bearing an established intracranial T9/9L glioma by combining a T9/9L glioma vaccine, which expresses the membrane form of macrophage colony stimulating factor (mM-CSF), and an anti-angiogenic drug-based therapy targeting growth factor receptors within the tumor's vasculature. The anti-angiogenic drugs included DMBI [a platelet derived growth factor receptor β and a fibroblast growth factor receptor 1 kinase inhibitor] and oxindole [a vascular endothelial growth factor receptor 2 kinase inhibitor]. Twenty to forty percent of the animals treated with the anti-angiogenic drugs alone survived. All non-treated controls and tumor vaccine- treated rats died within 40 days. In vitro, the drugs inhibited the endothelial cell formation of tubes and sprouts; they inhibited endothelial cells from proliferating in response to the angiogenic factors produced by T9/9L glioma cells. The drugs had no effect upon glioma cell growth or T cell mitogenesis. Animals that rejected the established T9/9L glioma by means of the combination therapy proved immune to an intracranial rechallenge by T9/9L glioma, but not to an unrelated MADB106 breast cancer. Anti-angiogenic drugs such as epigallocatechin gallate and thalidomide failed to enhance the tumor vaccine. This works demonstrates that particular anti-angiogenic drugs can successfully synergize with an mM-CSF-based tumor vaccine to treat more advanced tumors.