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© Institut Pasteur
Cristaux de cellulase, enzyme purifiée de Clostridium thermocellum permettant la digestion de la cellulose. Image colorisée.
Publication : Cancer research

A fully synthetic immunogen carrying a carcinoma-associated carbohydrate for active specific immunotherapy

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cancer research - 01 Apr 1999

Lo-Man R, Bay S, Vichier-Guerre S, Dériaud E, Cantacuzène D, Leclerc C

Link to Pubmed [PMID] – 10197623

Cancer Res. 1999 Apr;59(7):1520-4

Aberrant glycosylation of mucins leads to the exposure of cryptic carbohydrate antigens at the surface of carcinoma cells, which, therefore, represent potent targets for anticancer therapeutic vaccines. To date, the development of immunogens to stimulate immune response to such saccharidic antigens is based on carbohydrate conjugation to carrier proteins. However, these traditional protein conjugates are poorly defined in chemical composition and structure. As an alternative, we synthesized a multiple antigenic O-linked glycopeptide (MAG) carrying the carbohydrate Tn antigen associated with a CD4+ T-cell epitope (MAG:Tn-PV). This fully synthetic immunogen is highly defined in composition and carries a high saccharidic epitope ratio over the entire molecule. The MAG:Tn-PV was able to induce anti-Tn IgG antibodies that recognize human tumor cell lines. A therapeutic immunization protocol performed with this fully synthetic immunogen increased the survival of tumor-bearing mice. Thus, the accurately defined and versatile MAG system represents an efficient strategy to induce carbohydrate-specific antitumor immune responses but may also be applicable to the prevention of infectious diseases, if it is based on bacterial oligosaccharides.

http://www.ncbi.nlm.nih.gov/pubmed/10197623