Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with specific antitumor activities. It is selectively toxic for neuroblastoma (NB) cells in vitro with no significant effects on the viability of normal human cells. We evaluated the antitumoral effects of BS-RNase on human NB xenografts from UKF-NB-3 cells in athymic (nude) mice. The efficacy of direct intraneoplastic, subcutaneous and systemic delivery of BS-RNase was explored. Systemic 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 in the course of four weeks) and intratumoral BS-RNase treatment using the same schedule resulted in complete tumor regression. During 30 days following cessation of treatment no tumor regrowth was observed and animals were free of tumors. Toxic effects of BS-RNase (e.g., on bone marrow and inner organs) were not apparent. This data indicates that BS-RNase fulfills important criteria for a candidate antitumor agent specific for NB.

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