Growth arrest of solid human neuroblastoma xenografts in nude rats by natural IgM from healthy humans

Abstract

Neuroblastoma (NB) is the most common extracranial solid neoplasm of infancy and is associated with very poor prognosis in patients with advanced disease. 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 elusive. 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.

Increased immunoglobulin G, but not M, binding to endogenous retroviral antigens in HIV-1 infected persons

“…The physiological role of natural antibodies has not yet been determined. Speculatively, they could protect cells by blocking self epitopes, serve as primers for humoral immune responses to exogenous antigens [Ochsenbein et al, 1999], participate in the clearing of damaged and dead tissue [Guilbert et al, 1982;Naparstek et al, 1986], or mediate anti-cancer activity [David et al, 1996]. The repertoire of natural antibodies appears to be similar between healthy individuals [Guilbert et al, 1982;Avrameas et al, 1983].…”

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

“…57 Apparently, the titers of these anti-carbohydrate antibodies in neuroblastoma patients were negligible. 58,59 A successful treatment of neuroblastoma with these antibodies of healthy donors was performed in a nude rat model bearing solid human neuroblastoma tumors 57,60 and further in a small clinical study of nine neuroblastoma children patients suffering from late stage neuroblastoma. 61 Neuroblastoma patients had undergone several different treatments like chemotherapy, surgery, bone marrow transplantations and application of anti-GD2 monoclonal antibodies before they were included in this study.…”

Naturally Occurring Humoral Cytotoxicity Against Neuroblastoma (NB) Cells in Healthy Persons and Nb Patients

“…First experiments confirmed the expression of the 260-kDa antigen in human NB xenografts in nude rats [3] and demonstrated that natural anti-NB IgM obtained from positive human sera effects growth arrest of established human NB tumors [6]. Thus, natural anti-NB IgM may also have potential as a novel therapeutic modality in the treatment of human NB.…”