Natural human IgM antibodies in neuroblastoma therapy: Preliminary resultsfrom a phase I/II therapy study

Background: Sera from healthy individuals contain natural IgM antibodies (a nti-NB-Ab) cytotoxic to neuroblastoma (NB) cells. In contrast to healthy ch ildren the prevalence of anti-NB-Ab in sera of NB patients is low. Binding of anti-NB-Ab to the NB cell surface leads to activation of complement in v itro. In vitro the injection of the purified IgM fraction from a cytotoxic blood donor results in complete growth arrest of NB xenografts in nude rats . Preliminary results from a phase I/II study to evaluate the pharmacokinet ics and side effects of a therapy with anti-NB-Ab are presented here. Patients: Included in this study are patients with NB stage 4 according to INSS with relapse or non-responders to therapy according to the GPOH-NB-the rapy protocoll. The patients are negative for anti-NB-Ab and are older than one year. Methods: The therapy is based on a complete exchange of the anti-NB-Bb nega tive patient serum against serum from an anti-NB-Ab positive ABO-compatible donor by means of plasmapheresis. Results: Up to now, 14 cycles of plasmapheresis have been carried out in 6 NB patients. In 13 of 14 therapy cycles a significant increase in serum tox icity could be observed. Severe side effects have not been seen except a ca theter associated thrombosis which was reversible under heparin treatment. After plasmapheresis, pain in the tumor site or regions of metastasis did o ccur regularly. In some cases temporary elevation of body temperature occur red. One patient had a reduced MIBG uptake after therapy. Tumor necrosis wa s observed in 2 patients. Three patients showed tumor progress. Conclusion: Immunotherapy of NB in children by serum exchange using anti-NB -Ab positive ABO-compatible donor serum is feasible without major side effe cts and leads to a significant increase of serum toxicity against NB cells.