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Glycobiology Advance Access published online on March 20, 2007
Glycobiology, doi:10.1093/glycob/cwm028
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Glycoengineering of {alpha}Gal xenoantigen on recombinant peptide bearing the J28 pancreatic oncofetal glycotope

Marie-Odile Sadoulet2, Cécile Franceschi2, Muriel Aubert3, Françoise Silvy2, Jean-Paul Bernard2, Dominique Lombardo3 and Eric Mas1,2

2 Inserm UMR-777, Faculté de Médecine-Timone, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France; Université de la Méditerranée, Marseille, France ; Cancéropôle PACA, Marseille, France
3 Lung Cancer Biology Group, Cancer Research UK, Imperial College London, Hammersmith Hospitals Campus, London, UK

1 To whom correspondence should be adressed; e-mail : Eric.Mas{at}medecine.univ-mrs.fr

Received on October 25, 2006; revised on March 7, 2007; accepted on March 7, 2007

In human pancreatic adenocarcinoma alterations of glycosylation processes leads to the expression of tumor-associated-carbohydrate antigens representing potential targets for cancer immunotherapy. Among these pancreatic tumor-associated-carbohydrate antigens, the J28 glycotope located within O-glycosylated mucin-like C-terminal domain of the fetoacinar pancreatic protein (FAPP) and expressed at the surface of human tumoral tissues, can be a good target for anticancer therapeutic vaccines. However, the oncodevelopmental self character of the J28 glycotope associated to the low immunogenicity of tumor-associated-carbohydrate antigens may be a major obstacle to effective anti-tumor vaccine therapy. In this study, we have investigated a method to increase the immunogenicity of the recombinant pancreatic oncofetal J28 glycotope by glycoengineering {alpha}Gal epitope which may be recognized by natural anti-{alpha}Gal antibody present in humans. For this purpose, we have developed a stable CHO cell clone expressing {alpha}Gal epitope by transfecting the cDNA encoding the {alpha}1,3Galactosyltransferase. These cells have been previously equipped to produce the recombinant O-glycosylated C-terminal domain of FAPP carrying the J28 glycotope. As a consequence the C-terminal domain of FAPP produced by these cells carries out the {alpha}Gal epitope on oligosaccharide structures associated with the J28 glycotope. Furthermore, we show that this recombinant « {alpha}1,3galactosyl and J28 glycotope » may be targeted by human natural anti-{alpha}Gal antibodies but also by the mAbJ28 suggesting that the J28 glycotope remains accessible to the immune system as vaccinating agent. This approach may be used for many identified tumor-associated-carbohydrate antigens which can be glycoengineered to carry {alpha}Gal epitope to increase their immunogenicity and to develop therapeutic vaccines.

Key words: Pancreas / Cancer / Tumor-Associated-Carbohydrate Antigen / Glycotope / {alpha}Gal epitope / {alpha}1,3 Galactosyltransferase


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