Treatment of neuroblastoma with human natural antibodies

Serum of healthy individuals may contain natural antibodies which are able to induce complement dependent cytotoxicity against neuroblastoma. The prevalence of cytotoxic activity in serum of neuroblastoma patients is low compared with age matched healthy children which indicates a role of natural cytotoxic antibodies in immunosurveillance of neuroblastoma. Based on these findings we selected plasma of blood donors with a high in-vitro cytotoxic activity against LA-N-1 neuroblastoma cells. Using these plasma preparations a phase I/II therapy study in children with relapsed neuroblastoma based on a complete plasma exchange has been instituted. 34 plasma exchange cycles have been performed in nine patients. This therapy has been found to be feasible in all patients. In three patients a transient minor tumor response has been observed. In one patient stable disease could be established for 3 years. In another patient, who has got ten therapy cycles, disease-free survival is maintained for 8 years without any further therapy. Conclusion: The response data in patients with relapsed high-risk neuroblastoma justify the further evaluation of this immunotherapeutic approach. For this purpose a standardized pharmaceutical product generated by screening and pooling the plasma of selected blood donors would be of benefit.