title: Stable GM3 lactone mimetic raises antibodies specific for the antigens expressed on melanoma cells.
abstract: Immunotherapy of tumors and of melanoma in particular has a long history, and recently this therapeutic approach found a reliable scientific rationale. This biological therapy aims to teach the patient's immune system to recognize the antigens expressed on tumor cells and destroy them, leaving normal cells intact. The success of this therapy highly depends on the selection of target antigens that are essential for tumors growth and progression. The overexpression of GM(3) ganglioside 1 and especially the expression of its metabolite GM(3) lactone 2 characterize murine and human melanomas, playing an important role in tumor progression and making such self-antigens potential targets for the immunotherapy of these neoplasms. Although more immunogenic than its precursor, GM(3) lactone 2 is unsuitable to be used in immunotherapy as a melanoma-associated antigen (MAA) because it is unstable under physiological conditions. We designed and synthesized the hydrolytically stable mimetic 3, which is remarkably simpler than the native lactone 2; after conjugation of 3 to the protein carrier keyhole-limpet hemocyanin (KLH), the obtained glycoprotein 5 was used as the immunogen in vivo to successfully elicit specific antimelanoma antibodies. In fact, no appreciable binding to GM(1) was observed. Capitalizing on the stability and on the reduced structural complexity of mimetic 3, the immunostimulant 5 we report represents a new promising synthetic glycoconjugate for the immunotherapy of melanoma.
authors.affiliation: Dipartimento di Patologia e Oncologia Sperimentali, Universita' di Firenze, Florence, Italy. annarosa.arcangeli@unifi.it
authors.forename: Annarosa
authors.initials: A
authors.lastname: Arcangeli
authors.forename: Lucio
authors.initials: L
authors.lastname: Toma
authors.forename: Luca
authors.initials: L
authors.lastname: Contiero
authors.forename: Olivia
authors.initials: O
authors.lastname: Crociani
authors.forename: Laura
authors.initials: L
authors.lastname: Legnani
authors.forename: Carlotta
authors.initials: C
authors.lastname: Lunghi
authors.forename: Elisa
authors.initials: E
authors.lastname: Nesti
authors.forename: Gloriano
authors.initials: G
authors.lastname: Moneti
authors.forename: Barbara
authors.initials: B
authors.lastname: Richichi
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D002236:Carbohydrate Conformation; D003198:Computer Simulation; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006433:Hemocyanins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D005679:G(M3) Ganglioside; D006433:Hemocyanins; C047143:ganglioside GM3 lactone; C032808:keyhole-limpet hemocyanin