Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic antitumor properties

Rodriguez-Zhurbenko, Nely; Martinez, Darel; Blanco, Rances; Rondon, Teresa; Grinan, Tania; Maria Hernandez, Ana


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.

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Título según WOS: ID WOS:000316140600027 Not found in local WOS DB
Volumen: 43
Número: 3
Editorial: Wiley
Fecha de publicación: 2013
Página de inicio: 826
Página final: 837


Notas: ISI