Combined immunologic and anti-angiogenic therapy reduces hepatic micrometastases in a murine ocular melanoma model

Purpose : To evaluate the combined effect of neoadjuvant intracameral interferon alpha -2b and adjuvant low-dose angiostatin in reducing the number of hepatic micrometastases in a murine model of ocular melanoma. Methods : The posterior compartments of the right eyes of C57BL6 mice were inoculated with 5 x 10(5) cells/2.5 mu l of cells from the Queens, B16F10, or B16LS9 melanoma cell lines. The right eyes were enucleated at 7 days, and the mice were sacrificed at 28 days postinoculation, respectively. Hepatic micrometastases were counted. There were four treatment groups (n = 15 each) for each cell line as follows: group 1, intraperitoneal injections of 20 KIU interferon alpha -2b for 4 days prior to enucleation; group 2, intramuscular injections of 100 mu l 0.1 mu g/mu l murine angiostatin every day for 14 days starting on day 1 after enucleation; group 3, treatment of group 1 and group 2 combined; group 4, intraperitoneal and intramuscular injections of equal volumes of phosphate-buffered saline (PBS) (control group). Results : Results showed decreased micrometastases for groups 1 through 3 compared with group 4, with the greatest reduction in group 3 (p < 0.006). Conclusions: This study suggests that combined neoadjuvant interferon alpha-2b and adjuvant low-dose angiostatin therapy act synergistically to decrease hepatic micrometastases in a murine ocular melanoma model.