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Structural Glycobiology of Antibody Recognition in Xenotransplantation and Cancer Immunotherapy

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Anticarbohydrate Antibodies

Abstract

Carbohydrate antigens recognized by “natural” or preformed and elicited antibodies are central to transplantation/transfusion rejection across ABO blood group and species (xenotransplantation) barriers and are also promising candidates for cancer immunotherapy (Ramsland 2005). The key carbohydrate determinants (epitopes) recognized by antibodies are synthesized by a series of intracellular glycosyltransferases and are expressed on the surface of cells as glycolipids and glycoproteins. Often the minimal carbohydrate epitopes are located at the terminal end of more complex oligosaccharide chains, which result in these epitopes being displayed at a wide range of surface densities and contexts (e.g., glycolipids or glycoproteins). For example, many tumor-associated carbohydrate antigens are broadly expressed at very high densities on the cell surface of primary and metastatic tumors, but the same carbohydrates occur at much lower levels and are typically restricted to a few cell types in healthy tissues (Scott and Renner 2001; Ezzelarab et al. 2005; Kobata and Amano 2005; Cazet et al. 2010). Thus, antibodies with similar specificities for individual carbohydrate epitopes can display different and often selective cell-binding profiles, based on the unique presentation of the carbohydrates on the target cells.

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Acknowledgements

This work was funded in part by grants ID566722 and ID542512 from the National Health and Medical Research Council of Australia (NHMRC). M Agostino is a recipient of an Australian Postgraduate Award (APA). PA Ramsland was a recipient of an R Douglas Wright Career Development Award (ID365209) from the NHMRC. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute and the Ludwig Institute for Cancer Research.

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Authors and Affiliations

  1. Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia

    Mark Agostino & Elizabeth Yuriev

  2. Centre for Immunology, Burnet Institute, Melbourne, VIC, 3004, Australia

    William Farrugia & Paul A. Ramsland

  3. Department of Surgery Austin Health, University of Melbourne, Heidelberg, VIC, 3084, Australia

    Mauro S. Sandrin & Paul A. Ramsland

  4. Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne, VIC, 3084, Australia

    Andrew M. Scott

  5. Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, VIC, 3004, Australia

    Paul A. Ramsland

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  1. Mark Agostino
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  2. William Farrugia
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  3. Mauro S. Sandrin
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  4. Andrew M. Scott
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  5. Elizabeth Yuriev
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  6. Paul A. Ramsland
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Correspondence to Paul A. Ramsland .

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  1. , Department für Chemie, Universität für Bodenkultur Wien, Muthgasse 18, Wien, 1190, Austria

    Paul Kosma

  2. , Zentrum für Medizin und Biowissenschafte, Forschungszentrum Borstel, Parkallee 22, Borstel, 23845, Germany

    Sven Müller-Loennies

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Agostino, M., Farrugia, W., Sandrin, M.S., Scott, A.M., Yuriev, E., Ramsland, P.A. (2012). Structural Glycobiology of Antibody Recognition in Xenotransplantation and Cancer Immunotherapy. In: Kosma, P., Müller-Loennies, S. (eds) Anticarbohydrate Antibodies. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0870-3_9

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