Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Nature Medicine volume 2, pages 686–689 (1996)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Siegel, S.E. & Sato, J.K. Neuroblastoma. in Oncology, (eds. Moossa, A.R., Robson, M.C. & Schimpfl, S.C.) 1211–1231 (Williams St Wilkins, Baltimore, 1986).

    Google Scholar 

  2. Pinkerton, C.R. Neuroblastoma in the 1990s. A clinical perspective. in Human Neuroblastoma: Recent Advances in Clinical and Genetic Analysis. (eds. Schwab, M., Tonini, G.P. & Bénard, J.) 3–10 (Harwood Academic Publ., Chur, Switzerland, 1993).

    Google Scholar 

  3. Philip, T. & Pinkerton, R. Neuroblastoma. in New Directions in Cancer Treatment. (ed. Magrath, J.) 605–611 (Springer, Heidelberg, Germany, 1989).

    Chapter  Google Scholar 

  4. Ollert, M.W. et al. Normal human serum contains a natural IgM antibody cytotoxic for human neuroblastoma cells. Proc. Natl. Acad. Sci. U.S.A. (in the press).

  5. Dixon, F.J., Vasquez, J.J., Weigle, W.O. & Cochrane, C.G. Pathogenesis of serum sickness. Arch. Pathol. 65, 18–25 (1958).

    CAS  Google Scholar 

  6. Handgretinger, R. et al. The possible role of granulocytes in the therapy of neuroblastoma. in Human Neuroblastoma: Recent Advances in Clinical and Genetic Analysis. (eds. Schwab, M., Tonini, G.P. & Bénard, J.) 24–33 (Harwood Academic Publishers, Chur, Switzerland, 1993).

    Google Scholar 

  7. Bruchelt, G. et al. Effect of granulocytes on human neuroblastoma cells measured by chemiluminescence and chromium-51 release assay. J. Eiolumin. Chemilumin. 3, 93–96 (1989).

    Article  CAS  Google Scholar 

  8. Barker, E. et al. Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res. 51, 144–149 (1991).

    CAS  PubMed  Google Scholar 

  9. Barker, E. & Reisfeld, R.A. A mechanism for neutrophil-mediated lysis of human neuroblastoma cells. Cancer Res. 53, 362–367 (1993).

    CAS  PubMed  Google Scholar 

  10. Kushner, B.H. & Cheung, N.-K.V. GM-CSF enhances 3F8 monoclonal antibody-dependent cellular cytotoxicity against human melanoma and neuroblastoma. Blood 73, 1936–1941 (1989).

    CAS  PubMed  Google Scholar 

  11. Savill, J., Fadok, V., Henson, P. & Haslett, C. Phagocyte recognition of cells undergoing apoptosis. Immunol. Today 14, 131–136 (1993).

    Article  CAS  Google Scholar 

  12. Ouchterlony, Ö. & Nilsson, L.-Å. Immunodiffusion and immunoelectrophoresis. in Handbook of Experimental Immunology: Immunochemistry. 19.1–19.44 (ed. Weir, D.M.) (Blackwell Scientific Publ., Oxford, UK, 1978).

    Google Scholar 

  13. Vogel, C.-W. & Müller-Eberhard, H.J. Cobra venom factor: Improved method for purification and biochemical characterization. J. Immunol. Meth. 73, 203–220 (1984).

    Article  CAS  Google Scholar 

  14. Juhl, H. et al. A monoclonal antibody-cobra venom factor conjugate increases the tumor-specific uptake of a 99mTc-anti-CEA antibody by a two-step approach. Cancer Res. 55, 5749s–5755s (1995).

    CAS  PubMed  Google Scholar 

  15. Mujoo, K. et al. Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18. Cancer Res. 49, 2857–2861 (1989).

    CAS  PubMed  Google Scholar 

  16. Burck, H.-C. Physikalische und physikochemische Färbemethoden. in Histologische Technik. 104–141 (Georg Thieme, Stuttgart, Germany, 1988).

    Google Scholar 

  17. Laemmli, U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685 (1970).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany

    Kerstin David, Markus W. Ollert, Caren Vollmert, Carl-Wilhelm Vogel & Reinhard Bredehorst

  2. Department of Surgery, Christian-Albrechts-University Kiel, Amold-Heller-Strasse 7, 24105, Kiel, Germany

    Hartmut Juhl

  3. Department of Pediatric Oncology, University Hospital Eppendorf, University of Hamburg, Martinistrasse 52, 20246, Hamburg, Germany

    Rudolf Erttmann

Authors
  1. Kerstin David
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus W. Ollert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hartmut Juhl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Caren Vollmert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rudolf Erttmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carl-Wilhelm Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Reinhard Bredehorst
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

David, K., Ollert, M., Juhl, H. et al. Growth arrest of solid human neuroblastoma xenografts in nude rats by natural IgM from healthy humans. Nat Med 2, 686–689 (1996). https://doi.org/10.1038/nm0696-686

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0696-686

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing