Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic antitumor properties. Issue 3 (8th February 2013)

• Record Type: Journal Article
• Authors: Rodríguez‐Zhurbenko, Nely; Martínez, Darel; Blanco, Rancés; Rondón, Teresa; Griñán, Tania; Hernández, Ana María
• Is Part Of: European journal of immunology. Volume 43:Issue 3(2013:Mar.)
• Page Start: 826
• Page End: 837
• Publication Date: 2013-02-08
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242693
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>N‐</italic>glycolylated gangliosides are not naturally expressed in healthy human tissues but are overexpressed in several tumors. We demonstrate the existence of antibodies that bind (<italic>N‐</italic>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 <italic>N‐</italic>glycolylated gangliosides as antitumor targets.</p> </abstract>