Bovine seminal ribonuclease inhibits in vivo growth of human neuroblastomacells

Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with speci fic antitumor activities. Tt is selectively toxic for neuroblastoma (NB) ce lls in vitro with no significant effects on the viability of normal human c ells. We evaluated the antitumoral effects of BS-RNase on human NE xenograf ts from UKF-NB-3 cells in athymic (nude) mice. The efficacy of direct intra neoplastic, subcutaneous and systemic delivery of BS-RNase was explored. Sy stemic administration of BS-RNase (12.5 mg/kg/day intraperitoneally, for 20 days in the course of four weeks) suppressed tumor growth but was not able to induce any cures. Subcutaneous injections (12.5 mg/kg/day for 20 days i n the course of four weeks) and intratumoral BS-RNase treatment using the s ame schedule resulted in complete tumor regression. During 30 days followin g cessation of treatment no tumor regrowth was observed and animals were fr ee of tumors. Toxic effects of BS-RNase (e.g., on bone marrow and inner org ans) were not apparent. This data indicates that BS-RNase fulfills importan t ci criteria for a candidate antitumor agent specific for NB.