Evaluating Therapeutic Efficacy of the Vascular Disrupting Agent OXi8007 Against Kidney Cancer in Mice †

Background/Objectives: Vascular-disrupting agents promise significant therapeutic efficacy against solid tumors by selectively damaging tumor-associated vasculature. Methods: We have examined the efficacy of a water-soluble indole-based tubulin binding agent against kidney cancer. Results: Dynamic bioluminescence imaging (dBLI) and oxygen-enhanced multispectral optoacoustic tomography (OE-MSOT) both indicated rapid acute vascular shutdown following the administration of OXi8007 (250 mg/kg) in syngeneic orthotopic Renca-luc kidney tumors in mice, which continued over 24 h. MSOT similarly confirmed selective hypoxiation in human XP258 xenografts following OXi8007. Twice-weekly doses of OXi8007 alone caused no significant growth delay in Renca-luc tumors and did not enhance the tumor growth delay associated with cabozantinib, but they did significantly increase the median survival time for the combined treatment group. Meanwhile, twice-weekly doses of OXi8007 or cabozantinib alone significantly extended survival in the XP258 human xenograft tumors growing orthotopically in mice, though combination provided no additional benefit. The treatment of Renca-luc tumors with OXi8007 twice weekly with combined checkpoint inhibitors (CKIs) PD-1 and CTLA-4 improved survival over CKIs alone. Conclusion: These results verify the acute efficacy of OXi8007 in orthotopic kidney tumors, and long-term therapy indicates potency in some cases, with no overt toxicity.