title: Human antibodies reactive to NeuGcGM3 ganglioside have cytotoxic antitumor properties.
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.
authors: Tumor Immunology Direction, Center of Molecular Immunology, Havana, Cuba.
authors: Nely
authors: N
authors: Rodríguez-Zhurbenko
authors: Darel
authors: D
authors: Martínez
authors: Rancés
authors: R
authors: Blanco
authors: Teresa
authors: T
authors: Rondón
authors: Tania
authors: T
authors: Griñán
authors: Ana María
authors: AM
authors: Hernández
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D009336:Necrosis; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D005679:G(M3) Ganglioside; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C044298:N-glycolylneuraminyllactosylceramide