Aphidicolin glycinate inhibits human neuroblastoma cell growth in vivo

Aphidicolin is a fungal derived tetracyclic diterpene antibiotic. It is sel ectively toxic for neuroblastoma (NB) cells in vitro but has no significant effects on the viability of normal human cells and a variety of other tumo r entities. We evaluated the antitumoral effects of the water soluble ester aphidicolin glycinate (AphiG) on established human NE xenografts from UKF- NB-3 cells in athymic (nude) mice. Furthermore, we explored the efficacy of direct intraneoplastic and systemic delivery of AphiG. Systemic administra tion of AphiG (60 mg/kg intraperitoneally, twice per day on 10 consecutive days) significantly suppressed tumor growth but was not able to induce any cures. In contrast, intratumoral AphiG injections (60 or 40 mg/kg/twice a d ay for 4 days) induced complete tumor regression. Two weeks after the end o f treatment no tumor cells were microscopically detectable. Animals were fr ee of tumor for more than 90 days. Histologic examination of inner organs a nd bone marrow did not reveal any apparent toxic effects of AphiG. These da ta strongly indicate that AphiG deserves further evaluation as a specific t reatment for neuroblastoma.