Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic antitumor properties

Eur J Immunol. 2013 Mar;43(3):826-37. doi: 10.1002/eji.201242693. Epub 2013 Feb 8.


N-glycolylated gangliosides are not naturally expressed in healthy human tissues but are overexpressed in several tumors. We demonstrate the existence of antibodies that bind (N-glycolylneuraminyl)-lactosylceramide (NeuGcGM3) and are detectable in the sera of 65 from the 100 donors (65%) tested by ELISA. From those 65 NeuGcGM3 antibody-positive donors, 35 had antibodies that were able to recognize and kill NeuGcGM3-expressing tumor cells by a complement-mediated mechanism. After complement inactivation, 11 of the 35 positive sera showed a direct cytotoxic effect on the tumor cells. This complement-independent cytotoxicity was dependent on the presence of antigen on the membrane and resembles an oncotic necrosis cell death. Both the levels of anti-NeuGcGM3 antibodies in the sera as well as the percentage of healthy donors with this immunity decreased with the age of the donor. In contrast to age and gender-matched healthy donors, we could only detect low reactivity against NeuGcGM3 in the sera of six out of 53 non-small cell lung cancer patients. These results suggest the existence of antibodies against NeuGcGM3 with antitumor immune surveillance functions, reinforcing the importance of N-glycolylated gangliosides as antitumor targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Antibodies / pharmacology*
  • Antibodies / toxicity
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Female
  • G(M3) Ganglioside / analogs & derivatives*
  • G(M3) Ganglioside / immunology
  • G(M3) Ganglioside / metabolism
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Male
  • Mice
  • Necrosis
  • Neoplasms / immunology
  • Neoplasms / metabolism


  • Antibodies
  • Antineoplastic Agents
  • G(M3) Ganglioside
  • Immunoglobulin G
  • Immunoglobulin M
  • N-glycolylneuraminyllactosylceramide