A novel metastatic animal model reflecting the clinical appearance of human neuroblastoma: Growth arrest of orthotopic tumors by natural, cytotoxic human immunoglobulin M antibodies

Neuroblastoma (NE), the most common extracranial solid tumor in childhood i s associated with poor prognosis in patients with advanced tumor stages, Na tural human cytotoxic anti-NE IgM antibodies present in the serum of health y humans are discussed as a potential novel immunotherapeutic regimen again st human NB because these antibodies have been shown to affect growth arres t of solid s,c, xenografts of human NE in nude rats. Subcutaneously induced tumors, however, exhibit a different growth pattern compared with the typi cal growth pattern of NB tumors in humans. Therefore, we developed in this study a novel metastatic tumor model in nude rats that reflects the clinica l appearance of human NE and used this model to study the therapeutic effic acy of human anti-NE IgM. Intra-aortal injection of human NE cells in nude fats resulted in the development of large invasive adrenal gland tumors and micrometastases in the liver and bones. Apparently, adrenal glands provide most favorable growth conditions for human NE cells, as documented by the preferential and rapid growth of NB cells in this location, We studied thre e different treatment protocols of natural human anti-NE Ig;CI, Anti-NE IgM completely inhibited tumor formation and metastases when injected simultan eously with human LAN-I NE cells (P < 0,05), When antibody treatment was st arted 6 days after tumor cell injection (i.e., micrometastatic stage), tumo r growth was inhibited by 90% (P < 0,05), An anti-NE IgM therapy directed a gainst established tumors (14 days after tumor cell injection) shrank adren al gland tumors by 90% (P < 0,05), Analysis of the tumors revealed both com plement activation and an induction of apoptosis as two independent mechani sms of antitumor function. This study strongly suggests human anti-NE IgM a ntibodies as new agents for the therapy of neuroblastoma.