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International Immunology Advance Access published online on February 28, 2008
International Immunology, doi:10.1093/intimm/dxn011
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© The Author 2008. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Generation of tumour-rejecting anti-carbohydrate monoclonal antibodies using melanoma modified with Fas ligand

A. Katharina Simon1, Tom Newsom-Davis2,*, Matthew E. F. Frayne1,*, Paul F.-T. Ch’en1,2,*, Andrew J. McMichael1 and Gavin R. Screaton2

1 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
2 Department of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK

Correspondence to: Correspondence to: A. K. Simon; E-mail: katja.simon{at}ndm.ox.ac.uk

Carbohydrate antigens such as glycolipids and glycoproteins are over-expressed in a variety of cancers and have therefore been identified as ideal candidates for tumour vaccines. Detection of anti-carbohydrate antibodies is associated with a good prognosis in cancer patients. However, generation of an efficient adaptive immune response has been hampered by the low immunogenicity of carbohydrates due to tolerance. Here, we describe a method by which tumour-rejecting antibodies directed against carbohydrates can be elicited in two different melanoma mouse models. Thus, using the murine melanoma B16F10 over-expressing Fas ligand (FasL), we have generated mAbs against cancer carbohydrate antigens expressed by the melanoma. Importantly, passive transfer of mAbs resulted in rejection of melanoma in vivo. Their protective effect in vivo was dependent on FcR and in vitro antibody-dependent cellular phagocytosis. They were also able to delay tumour growth when injected after the tumour was established. FasL-expressing tumours as an adjuvant are a novel way to generate anti-carbohydrate antibodies able to reject tumours in vivo.

Keywords: carbohydrates, CD95 ligand, GM4, tolerance, tumour immunity

* These authors contributed equally to this study.

Transmitting editor: S. Nagata

Received 20 July 2007, accepted 23 January 2008.


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