Monoclonal Antibodies Against Gangliosides

  • L. Svennerholm
Conference paper
Part of the NATO ASI Series book series (volume 7)


A large number of murine monoclonal antibodies that react with gangliosides have been produced in the last few years. Most of them have been elicited by immunization with complex antigen mixtures, whole cells or tissue extracts, but recently some have been produced with pure gangliosides. Antibodies directed against carbohydrate determinants react with the sugar sequence linked either to lipid or peptide/protein. Since the gangliosides can be purified to homogeneity they are better suited as immunogens than glycoproteins, which often show microheterogeneity. Furthermore, carbohydrate antigens in glycoproteins are poorly immunogenic. Gangliosides are also more suitable than glycoproteins for use in establishing the epitope specificity (1). The antigenic determinant of monoclonal antibody 19-9 was determined with a ganglioside extract of the colon cancer used for the immunization, but the reactive antigen in the sera of cancer patients proved to be a mucin (2).


Murine Monoclonal Antibody Human Glioma Cell Line Monoclonal Antibody 18B8 Sugar Sequence Ganglioside Antigen 
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  1. 1.
    Svennerholm L (1984) Biological significance of gangliosides. in Dreyfus et al (eds) Cellular and pathological aspects of glycoconjugate metabolism. Inserm vol 126 pp 21–44.Google Scholar
  2. 2.
    Magnani JL, Steplewski Z, Koprowski H, Ginsburg V (1983) Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19–9 in the sera of patients as a mucin. Cancer Res 43: 5489.PubMedGoogle Scholar
  3. 3.
    Köhler G, Milstein C (1975) Continous cultures of fused cells secreting antibody of predestined specificity. Nature 256: 495–497.PubMedCrossRefGoogle Scholar
  4. 4.
    Solter D, Knowles BB (1978) Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1). Proc Natl Acad Sti USA 75: 5565–5569.CrossRefGoogle Scholar
  5. 5.
    Stern PL, Willison KR, Lennox E, Galfré G, Milstein C, Secher D, Ziegler A (1978) Monoclonal antibodies as probes for differentiation and tumor-associated antigens: A Forssman specificity on teratocarcinoma stem cells. Cell 14: 775–783.PubMedCrossRefGoogle Scholar
  6. 6.
    Eisenbarth GS, Walsh FS, Nirenberg M (1979) Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci USA 76: 4913–4917.PubMedCrossRefGoogle Scholar
  7. 7.
    Magnani JL, Brockhaus M, Smith DF, Ginsburg V, Blaszczyk M, Mitchell KF, Steplewski Z, Koprowski H (1981) A monosialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma. Science 212: 55–56.PubMedCrossRefGoogle Scholar
  8. 8.
    Pukel CS, Lloyd KO, Travassos LR, Dippold WG, Oettgen HF, Old LJ (1982) GD3… a prominent ganglioside of human melanoma. Detection and characterization by mouse monoclona antibody. J Exp Med 155: 1133–1147.PubMedCrossRefGoogle Scholar
  9. 9.
    Nudelman E, Hakomori S, Kannagi R, Levery S, Yeh M-Y, Hellström KE, Hellström I (1982) Characterization of a human melanoma-associated ganglioside antigen defined by a monoclonal antibody, 4.2. J Biol Chem 257: 12752–12756.PubMedGoogle Scholar
  10. 10.
    Kannagi R, Cochran NA, Ishigami F, Hakomori S, Andrews PW, Knowles BB, Solter D. (1983) Stage-specific embryonic antigens (SSEA-3 and 4) are epitopes of a unique globo-series ganglioside isolated from human teratocarcinoma cells. EMBO J 2: 2355–2361.PubMedGoogle Scholar
  11. 11.
    Lindholm L, Holmgren J, Svennerholm L, Fredman P, Nilsson O. Persson B. Myrvold H, Lagergård T (1983) Monoclonal antibodies against gastrointestinal tumor-associated antigens isolated as monosialogangliosides. Int Arch Allergy appl Immun 71: 178–181.CrossRefGoogle Scholar
  12. 12.
    Månsson J-E, Fredman P, Nilsson 0, Lindholm L, Holmgren J, Svennerholm L (1985) Chemical structure of carcinoma ganglioside antigens defined by monoclonal antibody C-50 and some allied gangliosides of human pancreatic adenocarcinoma. Biochim Biophys Acta 834: 110–117.PubMedGoogle Scholar
  13. 13.
    Fukushima K, Hirota M, Terasaki PI, Wakisaka A, Togashi H, Chia D, Suyama N, Fukushi Y, Nudelman E, Hakomori S (1984) Characterization of sialosylated Lewis as a new tumor-associated antigen. Cancer Res 44: 5279–5285.PubMedGoogle Scholar
  14. 14.
    Young WW, MacDonald EMS, Nowinski RC, Hakomori SY (1979) Production of monoclonal antibodies specific for distinct portions of the glycol ipid asíalo GM2 (gangliotriaosylceramide) J Exp Med 150: 1008–1019.PubMedCrossRefGoogle Scholar
  15. 15.
    Galanos C, Lüderitz O, Westphal O (1971) Preparation and properties of antisera against the lipid-A component of bacterial lipopolysaccharides Eur J Biochem 24: 116–122.PubMedCrossRefGoogle Scholar
  16. 16.
    Hakomori S, Patterson CM, Nudelman E, Sekiguchi K (1983) A monoclonal antibody directed to N-acetylneuraminosyl-α2–6 galactosyl residue in gangliosides and glycoproteins. J Biol Chem 258: 11819–11822.PubMedGoogle Scholar
  17. 17.
    Nilsson O, Lindholm L, Holmgren J, Svennerholm L (1985) Monoclonal antibodies raised against NeuAca2-6 neolactotetraosylceramide detect carcinoma associated gangliosides. Biochim Biophys Acta 835: 577–583.PubMedGoogle Scholar
  18. 18.
    Fredman P, Jeanson S, Lycke E, Svennerholm L (1985) A monoclonal antibody reacting specifically with ganglioside GD1b in human brain. FEBS letters 189: 23–26.PubMedCrossRefGoogle Scholar
  19. 19.
    Nudelman E, Fukushi Y, Levery SB, Hiquchi T, Hakomori S (1986) Novel fucolipids of human adenocarcinoma: disialosyl Lea antigen (III FucIII6 NeuAcIV6 NeuAcLC) of human colonic adenocarcinoma and the monoclonal antibody FH7) defining this structure. J Biol Chem 261: 5487–5495.PubMedGoogle Scholar
  20. 20.
    Feizi T (1981) Blood group li system: A carbohydrate antigen system defined by naturally monoclonal or oligoclonal autoantibodies of man. Immunol Commun 10: 127–156.PubMedGoogle Scholar
  21. 21.
    Hakomori S (1981) Blood group ABH and li antigens of human erythrocytes. Chemistry, polymorphism and their developmental change. Semin Hematol 18: 39–62.PubMedGoogle Scholar
  22. 22.
    Roeleke D, Pruzanski W, Ebert W, Romer W, Fischer R, Lenhard V, Rauterberg E (1980) A new human cold agglutinin Sa recognizing terminal N-acetylneuraminyl groups on the cell surface. Blood 55: 677–681.Google Scholar
  23. 23.
    Naiki M, Marcus DM (1977) Binding of N-acetylgalactosamine-containing compounds by a human IgM paraprotein. J Immunol 119: 537–539.PubMedGoogle Scholar
  24. 24.
    Kabat EA, Liao J, Shyong J, Osserman EF (1982) A monoclonal IgM macroglobulin with specificity for lacto-N-tetraose in a patient with bronchogenic carcinoma. J Immunol 128: 540–544.PubMedGoogle Scholar
  25. 25.
    O’Shannessy DJ, llyas AA, Dalakas MC, Mendell JR, Ouarles RH (1986) Specificity of human IgM monoclonal antibodies from patients with peripheral neuropathy. J Neuroimmunol 11: 131–136.PubMedCrossRefGoogle Scholar
  26. 26.
    Chou KH, llyas AA, Evans JE, Quarles RH, Jungalwala FB (1985) Structure of a glycolipid reacting with monoclonal IgM in neuropathy and with HNK-1. Biochem Biophys Res Communs 128: 383–388.CrossRefGoogle Scholar
  27. 27.
    IIyas AA, Quarles RH, Dalakas MC, Fishman PH, Braoly RO (1985) Monoclonal IgM in a patient with paraproteinemic polyneuropathy binds to gangliosides containing disialosyl groups. Ann Neruol 18: 655–659.CrossRefGoogle Scholar
  28. 28.
    Magnani JL, Nilsson B, Brockhaus M, Zopf D, Steplewski Z, Koprowski H, Ginsburg V (1982) A monoclonal antibody defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J Biol Chem 257: 14365–14369.PubMedGoogle Scholar
  29. 29.
    Nilsson O, Lindholm L, Månsson J-E, Holmgren J, Svennerholm L (1984) Carcinoma associated ganglioside antigens defined by monoclonal antibodies in Dreyfus et al (eds) Cellular and pathological aspects of glycoconjugate metabolism. Inserm vol 126 pp 495–512.Google Scholar
  30. 30.
    Uhlenbruck G, van Meensel-Maene U, Hanisch FG, Dienst C (1984) Unexpected occurrence of the Ca 19-9 tumor marker in normal human seminal plasma. Hoppe-Seyler’s Z Physiol Chem 365: 613–617.CrossRefGoogle Scholar
  31. 31.
    Nilsson O, Månsson J-E, Lindholm L, Holmgren J, Svennerholm L (1985) Sialosyllactotetraosylceramide, a novel ganglioside antigen detected in human carcinomas by a monoclonal antibody. FEBS Letters 182: 398–402.PubMedCrossRefGoogle Scholar
  32. 32.
    Månsson J-E, Fredman P, Bigner DD, Molin K, Rosengren B, Friedman HS, Svennerholm L (1986) Characterization of new gangliosides of the lactotetraose series in murine xenografts of a human glioma cell line. FEBS Letters 201: 109–113.PubMedCrossRefGoogle Scholar
  33. 33.
    Fukuda MN, Bothner B, Lloyd KO, Rettig WJ, Tiller PR, Dell A (1986) Structures of glycosphingolipids isolated from human embryonal carcinoma cells. The presence of mono- and disialosyIglycolipids with blood group type 1 sequence. J Biol Chem 261: 5145–5153.PubMedGoogle Scholar
  34. 34.
    Brockhaus M, Magnani JL, Herlyn M (1982) Monoclonal antibodies directed against the sugar sequence of lacto-N-fucopentaose III are obtained from mice immunized with human tumors. Arch Biochem Biophys 217: 647–651.PubMedCrossRefGoogle Scholar
  35. 35.
    Urdal DL, Brentnall TA, Bernstein ID, Hakomori S (1983) A granulocyte reactive monoclonal antibody IG10, identifies the Galβ1–4(Fucα1–3)-GlcNAc (X-deterrpinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules. Blood 62: 1022–1026.PubMedGoogle Scholar
  36. 36.
    Fukushi Y, Hakomori S, Nudleman E, Cochran N (1984) Novel fucolipids accumulating in human adenocarcinoma. II Selective isolation of hybridoma antibodies that differentially recognize mono-, di-, and trifucosylated type 2 chain. J Biol Chem 259: 4681–4685.PubMedGoogle Scholar
  37. 37.
    Brodin T, Hellström S, Hellström KE, Karlsson KA, Sjögren H-O, Strömberg N, Thurin J (1985) Mouse monoclonal antibodies with specificity for the melanoma-associated ganglioside disialyIlactosyI- ceramide (GD3) also react with the structural analogue disialylparagloboside. Biochem Biophys Acta 837: 349–353.PubMedGoogle Scholar
  38. 38.
    Cheresh DA, Varki AP, Varki NM, Stallcup WB, Levien J, Reisfeld RA (1984) A monoclonal antibody recognizes an O-acylated sialic acid in a human melanoma-associated ganglioside. J Biol Chem 259: 7453–7459.PubMedGoogle Scholar
  39. 39.
    Thurin J, Herlyn M, Hindsgaul O, Strömberg N, Karlsson KA, Elder D, Steplewski Z, Koprowski H (1985) Proton NMR and fast-atom bombardment mass spectrometry analysis of the melanoma-associated ganglioside 9-O-acetyl GD3. J Biol Chem 260: 14556–14563.PubMedGoogle Scholar
  40. 40.
    Grunwald GB, Fredman P, Magnani JL, Trisler D, Ginsburg V, Nirenberg, M (1985) Monoclonal antibody 18B8 detects gangliosides associated with neuronal differentiation and synapse formation. Proc Natl Acad Sci USA 82: 4008–4012.PubMedCrossRefGoogle Scholar
  41. 41.
    Dubois C, Magnani JL, Grunwald GB, Spitalnik SL, Trisler GD, Nirenberg M, Ginsburg V (1986) Monoclonal antibody 18B8 which detects synapse-associated antigens binds to ganglioside GT3 (II3(NeuAc)3 LcCer. J Biol Chem 261: 3826–3830.Google Scholar
  42. 42.
    Tai T, Paulson JC, Gahan LD, Irie RF (1983) Ganglioside GM2 as a human antigen (OFAI-1). Proc Natl Acad Sci USA 80: 5392–5396.PubMedCrossRefGoogle Scholar
  43. 43.
    Cahan LD, Irie Rl, Singh R, Cassidenti A, Paulsen JC (1982) Identification of human neuroectodermal tumor antigen (IA-l-2) as ganglioside GD2. Proc Natl Acad Sci USA 79: 7629–7633.PubMedCrossRefGoogle Scholar
  44. 44.
    Schulz G, Cheresh DA, Varki NM, Yu A, Staffileno LK, Reisfeld RA (1984) Detection of ganglioside GD2 in tumor tissues and neuroblastoma patients. Cancer Res 44: 5914–5920.PubMedGoogle Scholar
  45. 45.
    Fredman P, Brezicka T, Holmgren J, Lindholm L, Svennerholm L (1986) Binding specificity of monoclonal antibodies to ganglioside, Fuc-GM1. Biochim Biophys Acta 875: 316–323.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • L. Svennerholm
    • 1
  1. 1.Department of Psychiatry and NeurochemistryGothenburg University St. Jörgen HospitalHisings BackaSweden

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