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

Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic antitumor properties.

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  • 1Tumor Immunology Direction, Center of Molecular Immunology, Havana, Cuba.

Abstract

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.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID:
23319307
[PubMed - indexed for MEDLINE]
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