Nature Medicine
2, 686 - 689 (1996)
doi:10.1038/nm0696-686
Growth arrest of solid human neuroblastoma xenografts in nude rats by natural IgM from healthy humansKerstin David1, Markus W. Ollert1, Hartmut Juhl2, Caren Vollmert1, Rudolf Erttmann3, Carl-Wilhelm Vogel1
& Reinhard Bredehorst1
1Department of Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
2Department of Surgery, Christian-Albrechts-University Kiel, Amold-Heller-Strasse 7, 24105 Kiel, Germany
3Department of Pediatric Oncology, University Hospital Eppendorf, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany Neuroblastoma (NB) is the most common extracranial solid neoplasm of infancy and is associated with very poor prognosis in patients with advanced disease1,2. Current therapeutic regimens of advanced NB which combine surgical resection with radiation therapy and/or chemotherapy brought some improvements, but in a significant number of patients, a cure remains elusive3. Normal human serum of healthy adults contains natural IgM antibodies that are cytotoxic for human NB cells. In this study, we evaluated the anti−NB activity of these natural IgM antibodies in nude rats bearing solid human NB tumors. A single intravenous (i.v.) injection of purified cytotoxic IgM led to uptake of IgM into the tumors with massive perivascular complement activation and accumulation of neutrophil granulocytes after 24 hours. Five consecutive i.v. injections of purified cytotoxic IgM into NB−bearing animals resulted in complete growth arrest of even large and established solid tumors which lasted for several weeks after discontinuation of the injections, whereas tumors of control animals continued to grow exponentially during the observation period. These studies suggest that natural anti−NB IgM may have a potential as a novel therapeutic modality in the treatment of human NB.
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