Abstract
Carbohydrate tumor antigens on glycoproteins and glycolipids are targets for active and passive cancer immunotherapy. These highly abundant antigens are de novo expressed or up-regulated due to changes in the complex glycosylation apparatus of tumor cells, involving sets of enzymes like glycosyltransferases, glycosidases, epimerases, and nucleotide sugar transporters. Various lipid or protein bound carbohydrate tumor antigens are described, for example, GM2, GD2, GD3, fucosylated GM1, Globo H, LeY, Lea, Sialyl-Lea and the mucin core structures Tn, Sialyl-Tn, and the Thomsen-Friedenreich Antigen (TF). Carbohydrate tumor antigens are far more abundant than protein tumor antigens rendering them suitable targets especially for antibodies, for example, highly expressed protein tumor markers as Her-2/neu express about 106 and TF about 107 copies per cell. More recent data show that certain carbohydrate structures are not only targets for humoral but also cellular immune responses.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Abdel-Motal, U.M., Berg, L., Rosen, A., Bengtsson, M., Thorpe, C.J., Kihlberg, J., Dahmen, J., Magnusson, G., Karlsson, K.A., and Jondal, M., 1996, Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells, Eur. J. Immunol. 26(3):544–551.
Adluri, S., Helling, F., Ogata, S., Zhang, S., Itzkowitz, S.H., Lloyd, K.O., and Livingston, P.O., 1995, Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients, Cancer Immunol Immunother. 41(3):185–192.
Baldus, S.E., Hanisch, F.-G., Kotlarek, G.M., Zirbes, T.K., Thiele, J., Isenberg, J., Karsten, U., Devine, P.L., and Dienes, H.P., 1998, Coexpression of MUC1 mucin peptide core and the Thomsen-Friedenreich antigen in colorectal neoplasms, Cancer. 82:1019–1027.
Baldus, S.E., Hanisch, F.G., Monaca, E., Karsten, U., Zirbes, T.K., Thiele, J., and Dienes, H.P., 1999, Immunoreactivity of Thomsen-Friedenreich (TF) antigen in human neoplasms: the importance of carrier-specific glycotope expression on MUC1, His toi Histopathol 14:1153–1158.
Baldus, S.E., Zirbes, T.K., Hanisch, F.-G., Kunze, D., Shafizadeh, S.T., Nolden, S., Mönig, S.P., Schneider, P.M., Karsten, U.R., Thiele, J., Hölscher, A.H., and Dienes, H.P., 2000, Thomsen-Friedenreich (TF) antigen presents as a prognostic factor in colorectal carcinoma: a clinico-pathological study including 264 patients, Cancer. 88:1536–1543.
Baldus, S.E., Zirbes, T.K., Glossmann, J., Fromm, S., Hanisch, F.-G., Mönig, S.P., Schröder, W., Schneider, P.M., Flucke, U., Karsten, U., Thiele, J., Hölscher, A.H., and Dienes, H.P., 2001, Immunoreactivity of monoclonal antibody BW835 represents a marker of progression and prognosis in early gastric cancer, Oncology. 61:147–155.
Beuth, J., Ko, H.L., Schirrmacher, V., Uhlenbruck, G., and Pulverer, G., 1988, Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan, Clin Expl Metastasis. 6:115–120.
Brockhausen, I., 2000, O-linked chain glycosyltransferases, Methods Mol Biol. 125:273–293.
Brockhausen, I., Romero, P.A., and Herscovics, A., 1991, Glycosyltransferase changes upon differentiation of CaCo-2 human colonic adenocarcinoma cells, Cancer Res. 51(12):3136–3142.
Brockhausen, I., Yang, J.M., Burchell, J., Whitehouse, C., and Taylor-Papadimitriou, J., 1995, Mechanisms underlying aberrant glycosylation of MUC1 mucin in breast cancer cells, Eur J Biochem. 233(2):607–617.
Butschak, G. and Karsten, U., 2002, Isolation and characterization of Thomsen-Friedenreich-specific antibodies from human serum, Tumor Biol. 23:113–122.
Cao, Y., Blohm, D., Ghadimi, B.M., Stosiek, P., Xing, P.X., and Karsten, U., 1997a, Mucins (MUC1 and MUC3) of gastrointestinal and breast epithelia reveal different and heterogeneous tumor-associated aberrations in glycosylation, J Histochem Cytochem. 45(11):1547–1557.
Cao, Y., Karsten, U., Liebrich, W., Haensch, R., Springer, G.F., and Schlag, P., 1995, Expression of Thomsen-Friedenreich-related antigens in primary and metastatic colorectal carcinomas: a reevaluation, Cancer. 76:1700–1708.
Cao, Y., Karsten, U., Otto, G., and Bannasch, P., 1999, Expression of MUC1, Thomsen-Friedenreich antigen, Tn, sialosyl-Tn, and α2,6-linked sialic acid in hepatocellular carcinomas and preneoplastic hepatocellular lesions, Virchows Arch. 434:503–509.
Cao, Y., Karsten, U., Zerban, H., and Bannasch, P., 2000, Expression of MUC1, Thomsen-Friedenreich-related antigens, and cytokeratin 19 in human renal cell carcinomas and tubular clear cell lesions, Virchows Arch. 436:119–126.
Cao, Y., Karsten, U., and Schwartz-Albiez, R., 2002, Expression of Thomsen-Friedenreich-related carbohydrate antigens on human leukemia cells, in: Leucocyte Typing VII, D. Mason et al., Eds., Oxford University Press, Oxford, pp. 204–205.
Cao, Y., Schlag, P.M., and Karsten, U., 1997b, Immunodetection of epithelial mucin (MUC1, MUC3) and mucin-associated glycotopes (TF, Tn, and sialosyl-Tn) in benign and malignant lesions of colonic epithelium: apolar localization corresponds to malignant transformation, Virchows Arch. 431:159–166.
Cao, Y., Stosiek, P., Springer, G.F., and Karsten, U., 1996, Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues: a systematic and comparative study, Histochem Cell Biol. 106:197–207.
Clausen, H., Stroud, M., Parker, J., Springer, G., and Hakomori, S., 1988, Monoclonal antibodies directed to the blood group A associated structure, galactosyl-A: specificity and relation to the Thomsen-Friedenreich antigen, Mol Immunol. 25(2):199–204.
Desai, P.R., Ujjainwala, L.H., Carlstedt, S.C., and Springer, G.F., 1995, Anti-Thomsen-Friedenreich (T) antibody-based ELISA and its application to human breast carcinoma detection, J Immunol Methods. 188:175–185.
Engelsberg, A., Hermosilla, R., Karsten, U., Shulein, R., Dorken, B., and Rehm, A., 2003, The Golgi protein RCAS1 controls cell surface expression of tumor-associated O-linked glycan antigens. J Biol Chem. 278(25):22998–23007. Epub 2003 Apr 02.
Friedenreich, V., 1930, The Thomsen Haemagglutiantion Phenomenon, Levin & Munksgaard, Copenhagen.
Galli-Stampino, L., Meinjohanns, E., Frische, K., Meldal, M., Jensen, T., Werdelin, O., and Mouritsen, S., 1997, T-cell recognition of tumor-associated carbohydrates: the nature of the glycan moiety plays a decisive role in determining glycopeptide immunogenicity, Cancer Res. 57(15):3214–3222.
Ghazizadeh, M., Kagawa, S., Izumi, K., and Kurokawa, K., 1984, Immunohistochemical localization of antigen-like substance in benign hyperplasia and adenocarcinoma of the prostate, J Urol. 132:1127–1130.
Glinsky, V.V., Glinsky, G.V., Rittenhouse-Olson, K., Huflejt, M.E., Ginskii, O.V., Deutscher, S.L., and Quinn, T.P., 2001, The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium, Cancer Res. 61(12):4851–4857.
Goletz, S., Thiede, B., Hanisch, F.G., Schultz, M., Peter-Katalinic, J., Muller, S., Seitz, O., and Karsten, U., 1997, A sequencing strategy for the localization of O-glycosylation sites of MUC1 tandem repeats by PSD-MALDI mass spectrometry. Glycobiology. 7(7):881–896.
Hassan, H., Reis, C.A., Bennett, E.P., Mirgorodskaya, E., Roepstorff, P., Hollingsworth, M.A., Burchell, J., Taylor-Papadimitriou, J., and Clausen, H., 2000, The lectin domain of UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-T4 directs its glycopeptide specificities, J Biol Chem. 275(49):38197–38205.
Haurum, J.S., Arsequell, G., Lellouch, A.C., Wong, S.Y., Dwek, R.A., McMichael, A.J., and Elliott, T., 1994, Recognition of carbohydrate by major histocompatibility complex class I-restricted, glycopeptide-specific cytotoxic T lymphocytes, J Exp Med. 180(2):739–744.
Hull, S.R., and Carraway, K.L., 1988, Mechanism of expression of Thomsen-Friedenreich (T) antigen at the cell surface of a mammary adenocarcinoma, FASEB J. 2(8):2380–2384.
Irazoqui, F.J., Jansson, B., Lopez, P.H., and Nores, G.A., 2001, Correlative fine specificity of several Thomsen-Friedenreich disaccharide-binding proteins with an effect on tumor cell proliferation, J Biochem (Tokyo). 130(1):33–37.
Itzkowitz, S.H., Yuan, M., Montgomery, C.K., Kjeldsen, T, Takahashi, H.K., Bigbee, W.L., and Kim, Y.S., 1989, Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer, Cancer Res. 49(1):197–204.
Jeschke, U., Richter, D.U., Hammer, A., Briese, V., Friese, K., and Karsten, U., 2002, Expression of the Thomsen-Friedenreich antigen and of its putative carrier protein mucin 1 in the human placenta and in trophoblast cells in vitro, Histochem Cell Biol. 117:219–226.
Karsten, U., Butschak, G., Cao, Y., Goletz, S., and Hanisch, F.-G., 1995, A new monoclonal antibody (A78-G/A7) to the Thomsen-Friedenreich pan-tumor antigen, Hybridoma. 14:37–44.
Karsten, U., 2002, CD176 Workshop Panel report, in: Leucocyte Typing VIL D. Mason et al., Eds., Oxford University Press, Oxford, pp. 202–203.
Klenk, E. and Uhlenbruck, G., 1960, Über neuraminsäurehaltige Mucoide aus Menschenerythrocytenstroma, ein Beitrag zur Chemie der Agglutinogene, Z Physiol Chem. 319:151–160.
Kumamoto, K., Goto, Y., Sekikawa, K., Takenoshita, S., Ishida, N., Kawakita, M., and Kannagi, R., 2001, Increased expression of UDP-galactose transporter messenger RNA in human colon cancer tissues and its implication in synthesis of Thomsen-Friedenreich antigen and sialyl Lewis A/X determinants, Cancer Res. 61(11):4620–4627.
Livingston, P.O. and Lloyd, K.O., 2000, Carbohydrate antigens on glycolipids and glycoproteins, Principles and practice of the biologic therapy of cancer, Rosenberg, S.A., 3rd edn, Lippincott Williams & Wilkins.
Muller, S., Goletz, S., Packer, N., Gooley, A., Lawson, A.M., and Hanisch, F.G., 1997, Localization of O-glycosylation sites on glycopeptide fragments from lactation-associated MUC1. All putative sites within the tandem repeat are glycosylation targets in vivo, J Biol Chem. 272(40):24780–24793.
Rottger, S., White, J., Wandall, H.H., Olivo, J.C., Stark, A., Bennett, E.P., Whitehouse, C., Berger, E.G., Clausen, H., and Nilsson, T., 1998, Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus, J Cell Sci. 111(Pt 1):45–60.
Rudd, P.M., Elliott, T., Cresswell, P., Wilson, I.A., and Dwek, R.A., 2001, Glycosylation and the immune system, Science. 291(5512):2370–2376.
Schachter, H., 1986, Biosynthetic controls that determine the branching and microheterogeneity of protein-bound oligosaccharides, Biochem Cell Biol. 64(3):163–181.
Schlepper-Schafer, J. and Springer, G.F., 1989, Carcinoma autoantigens T and Tn and their cleavage products interact with Gal/GalNAc-specific receptors on rat Kupffer cells and hepatocytes, Biochim Biophys Acta. 1013(3):266–272.
Schneider, E, Kemmner, W., Haensch, W., Franke, G., Gretschel, S., Karsten, U., and Schlag, P.M., 2001, Overexpression of sialyltransferase CMP-sialic acid: Galbeta 1,3 GalNAc-R alpha6-Sialyltransferase is related to poor patient survival in human colorectal carcinomas, Cancer Res. 61(11):4605–4611.
Schwientek, T., Bennett, E.P., Flores, C., Thacker, J., Hollmann, M., Reis, C.A., Behrens, J., Mandel, U., Keck, B., Schafer, M.A., Haselmann, K., Zubarev, R., Roepstorff, P, Burchell, J.M., Taylor-Papadimitriou, J., Hollingsworth, M.A., and Clausen, H., 2002, Functional conservation of subfamilies of putative UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyltransferases in Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of 1(2)35Aa is essential in Drosophila J Biol Chem. 277(25):22623–22638.
Shamsuddin, A.M. and Elsayed, A.M., 1988, A test for detection of colorectal cancer, Human Pathol. 19:7–10.
Shigeoka, H., Karsten, U., Okuno, K., and Yasutomi, M., 1999, Inhibition of liver metastases from neuraminidase-treated Colon 26 cells by an anti-Thomsen-Friedenreich-specific monoclonal antibody, Tumor Biol. 20:139–146.
Singh, R., Campbell, B.J., Yu, L.G., Fernig, D.G., Milton, J.D., Goodlad, R.A., FitzGerald, A.J., and Rhodes, J.M., 2001, Cell surface-expressed Thomsen-Friedenreich antigen in colon cancer is predominantly carried on high molecular weight splice variants of CD44, Glycobiology. 11(7):587–592.
Speir, J.A., Abdel-Motal, U.M., Jondal, M., and Wilson, I.A., 1999, Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL, Immunity. 10(1):51–61.
Springer, G.F., 1984, T and Tn, general carcinoma autoantigens, Science. 224:1198–1206.
Springer, G.F., 1997, Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy, J Mol Med. 75:594–602.
Springer, G.F., Desai, P.R., and Banatwala, I., 1975, Blood group MN antigens and precursors in normal and malignant human breast glandular tissue, J Natl Cancer Inst. 54:335–339.
Springer, G.F. and Tegtmeyer, H., 1981, Origin of anti-Thomsen-Friedenreich (T) and Tn agglutinins in man and White Leghorn chicks, Br J Haematol. 47:453–460.
Stahn, R. and Zeisig, R., 2000, Cell adhesion inhibition by glycoliposomes: effects of vesicle diameter and ligand density, Tumour Biol. 21(3):176–186.
Stein, R., Chen, S., Grossman, W., and Goldenberg, D.M., 1989, Human lung carcinoma monoclonal antibody specific for the Thomsen-Friedenreich antigen, Cancer Res. 49(1):32–37.
Steuden, I., Duk, M., Czerwinski, M., Radzikowski, C., and Lisowska, E., 1985, The monoclonal antibody anti-asialoglycophorin from human erythrocytes specific for beta-D-Gal-1-3-alpha-D-GalNac-chains (Thomsen-Friedenreich receptors), Glycoconjugate J. 2:303–314.
Takanami, I., 1999, Expression of Thomsen-Friedenreich antigen as a marker of poor prognosis in pulmonary adenocarcinoma, Oncol. Rep. 6(2):341–344.
Yu, L.G., Milton, J.D., Fernig, D.G., and Rhodes, J.M., 2001, Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins, J Cell Physiol. 186(2):282–287.
Wandall, H.H., Hassan, H., Mirgorodskaya, E., Kristensen, A.K., Roepstorff, P., Bennett, E.P., Nielsen, P.A., Hollingsworth, M.A., Burchell, J., Taylor-Papadimitriou, J., and Clausen, H., 1997, Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1,-T2, and-T3, J Biol Chem. 272(38):23503–23514.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this paper
Cite this paper
Goletz, S., Cao, Y., Danielczyk, A., Ravn, P., Schoeber, U., Karsten, U. (2003). Thomsen-Friedenreich Antigen: The “Hidden” Tumor Antigen. In: Axford, J.S. (eds) Glycobiology and Medicine. Advances in Experimental Medicine and Biology, vol 535. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0065-0_10
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0065-0_10
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4908-2
Online ISBN: 978-1-4615-0065-0
eBook Packages: Springer Book Archive