IFN- α 2b and Thalidomide Synergistically Inhibit Tumor-Induced Angiogenesis

Angiogenesis is an absolute requirement for tumor growth and metastasis. The purpose of this study was to evaluate the antiangiogenic activity of interferon-α2b (IFN-α2b) and thalidomide, as single agents and in combination. The murine dermis model was used to assess tumor-induced angiogenesis in nude mice. Human ACHN (renal), NIH-OVCAR-3 (ovarian), LNCaP (prostate), and SK-Mel-1 (melanoma) tumor cells were inoculated intradermally into the flanks of nude mice. IFN-α2b and thalidomide, administered daily, were effective inhibitors of angiogenesis induced by all four tumor types. The combination of IFN-α2b and thalidomide caused a synergistic decrease in mean vessel count in tumors that were resistant to the antiproliferative effects of IFN-α2b and thalidomidein vitro. This enhanced suppression of angiogenesis translated into synergistic antitumor activity in a xenograft model. Pegylated IFN-α (PEG-IFN-α2b) (10⁶ U) administered once in 10 days was as effective as daily IFN-α2b treatment (10⁶ U × 10 days). IFN-α2b and thalidomide have potentiated antiangiogenic activity when used in combination. A single dose of PEG-IFN-α2b (10⁶ U) was as effective at suppressing vessel growth as an equivalent dose of IFN-α2b given daily for 10 days.