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 GM3 ganglioside 1 and especially the expression of its metabolite GM3 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, GM3 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 GM1 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.

Stable GM3 lactone mimetic raises antibodies specific for the antigens expressed on melanoma cells / Arcangeli A.; Toma L.; Contiero L.; Crociani O.; Legnani L.; Lunghi C.; Nesti E.; Moneti G.; Richichi B.; Nativi C.. - In: BIOCONJUGATE CHEMISTRY. - ISSN 1043-1802. - STAMPA. - 21:(2010), pp. 1432-1438. [10.1021/bc900557v]

Stable GM3 lactone mimetic raises antibodies specific for the antigens expressed on melanoma cells

ARCANGELI, ANNAROSA;CROCIANI, OLIVIA;MONETI, GLORIANO;RICHICHI, BARBARA;NATIVI, CRISTINA
2010

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 GM3 ganglioside 1 and especially the expression of its metabolite GM3 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, GM3 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 GM1 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.
21
1432
1438
Arcangeli A.; Toma L.; Contiero L.; Crociani O.; Legnani L.; Lunghi C.; Nesti E.; Moneti G.; Richichi B.; Nativi C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/394726
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