Ganglioside antigens in tissue sections of skin, naevi, and melanoma — Implications for treatment of melanoma

  • Peter Hersey
Part of the Cancer Treatment and Research book series (CTAR, volume 54)


Ganliosides were first described by Ernst Klenk in 1936 as a class of glycolipid-containing sialic acids that were found in brain tissue [1]. It is now known that they are components of cells in most tissues and that they are synthesized by glycosyltransferases in the plasma membrane, Golgi apparatus, and microsomes of cells [1,2]. They appear to serve as receptors for products such as cholera and tetanus toxin [2], viruses [3,4], and hormones, such as thyroid-stimulating hormone [2], serotonin [2], interleukin-2 (IL-2) [5], and interferon [2]. They appear to have an important role in cell membranes in either enhancing [6] or inhibiting signal transduction resulting from receptor interactions with a variety of growth factors, such as epidermal growth factor, fibroblast growth factor, and platelet-derived growth factors [6, 7, 8]. In some tissues they appear to be associated with activation of Ca2+-dependent protein kinases [9] and Ca2+-flux across cell membranes [10].


Melanoma Cell Sialic Acid Metastatic Melanoma Primary Melanoma Human Melanoma Cell 
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  1. 1.
    Hakamori, S. (1986) Glycosphingolipids. Sci. Am. May:32–41.Google Scholar
  2. 2.
    Fishman, P.H., Brady, R.O. (1976) Biosynthesis and function of gangliosides. Science 194:906–915.PubMedCrossRefGoogle Scholar
  3. 3.
    Markwell, M.A.K., Svennerholm, L., Paulson, J.C. (1981) Specific gangliosides function as host cell receptors for Sendai virus. Proc. Natl. Acad. Sci. USA 78:5406–5410.PubMedCrossRefGoogle Scholar
  4. 4.
    Bergelson, L.D., Bukrinskaya, A.G., Prokazova, N.V. et al. (1982) Role of gangliosides in reception of influenza virus. Eur. J. Biochem. 128:467–474.PubMedCrossRefGoogle Scholar
  5. 5.
    Robb. R.J. (1986) The suppressive effect of gangliosides upon IL2-dependent proliferation as a function of inhibition of IL2 receptor association. J. Immunol. 136:971.PubMedGoogle Scholar
  6. 6.
    Speigel, S., Fishman, P.H. (1987) Gangliosides as bimodal regulators of cell growth. Proc. Natl. Acad. Sci. USA 84:141–145.CrossRefGoogle Scholar
  7. 7.
    Bremer, E.G., Schlessinger, J., Hakamori, S. (1986) Gangliosides mediated modulation of cell growth. Specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor. J. Biol. Chem. 261:2434–2340.PubMedGoogle Scholar
  8. 8.
    Bremer, E.G., Hakamori, S. (1982) GM3 ganglioside induces hamster fibroblast growth inhibition in chemically defined medium: Ganglioside may regulate growth factor receptor function. Biochem. Biophys. Res. Commun. 106:711–718.PubMedCrossRefGoogle Scholar
  9. 9.
    Goldenring, J.R., Otis, L.C., Yu, R.K., DeLorenzo, R.J. (1985) Calcium/ganglioside-dependent protein kinase activity in rat brain membrane. J. Neurochem. 44:1229–1234.PubMedCrossRefGoogle Scholar
  10. 10.
    Spiegel, S., Panagiotopoulous, C. (1988) Mitogenesis of 3T3 fibroblasts induced by endogenous ganglioside is not mediated by cAMP, protein kinase C, or phosphoinositides turnover. Exp. Cell Res. 177(2):414–427.PubMedCrossRefGoogle Scholar
  11. 11.
    Ravindranath, M.H., Irie, R.F. (1988) Gangliosides as antigens of human melanoma. In: Nathanson, L. ed., Cancer Treatment and Research, Vol. 4. Kluwer Academic, Norwell, MA.Google Scholar
  12. 12.
    Pukel, C.S., Lloyd, K.O., Travassos, L.R., et al. (1982) GD3, a prominent ganglioside of human melanoma. J. Exp. Med. 155:1133–1147.PubMedCrossRefGoogle Scholar
  13. 13.
    Portoukalian, J., Zwingelstein, G., Dore, J.F. (1979) Lipid composition of human malignant melanoma tumors at various levels of malignant growth. Eur. J. Biochem. 94:19–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Cheresh, D.A., Varki, A.P., Varki, N.M., Stallcup, W.B., Levine, J., Reisfeld, R.A. (1984) A monoclonal antibody recognizes an O-acetyl sialic acid in a human melanoma-associated ganglioside. J. Biol. Chem. 259:7453–7459.PubMedGoogle Scholar
  15. 15.
    Furukawa, K., Chait, B.T., Lloyd, K.O. (1988) Identification of N-glycolylneuraminic acid-containing gangliosides of cat and sheep erythrocytes. J. Biol. Chem. 263:14939–14947.PubMedGoogle Scholar
  16. 16.
    Hellstrom, I., Brankojan, V., Hellstrom, K.E. (1985) Strong antitumor activities of IgG3 antibodies to a human melanoma associated ganglioside. Proc. Natl. Acad. Sci. USA 82: 1499–1502.PubMedCrossRefGoogle Scholar
  17. 17.
    Cheresh, D.A., Harper, J.R., Schulz, G., Reisfeld, R.A. (1984) Localization of the gangliosides GD2 and GD3 in adhesion plaques and on the surface of human melanoma cells. Proc. Natl. Acad. Sci. USA 81:5767–5771.PubMedCrossRefGoogle Scholar
  18. 18.
    Thurin, J., Thurin, M., Herlyn, M., et al. (1986) GD2 ganglioside biosynthesis is a distinct biochemical event in human melanoma tumor progression. FEBS Lett. 208:17–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Hirabayashi, Y., Hamaoka, A., Matsumoto, M., et al. (1985) Syngenetic monoclonal antibody against melanoma antigens with interspecies cross-reactivity recognizes GM3, a prominent ganglioside of B16 melanoma. J. Biol. Chem. 260:13328–13333.PubMedGoogle Scholar
  20. 20.
    Tai, T., Paulson, J.C., Cahan, L.D., Irie, R.F. (1983) Ganglioside GM2 as a human tumor antigen (OFA-1-1). Proc. Natl. Acad. Sci. USA 80:5392–5396.PubMedCrossRefGoogle Scholar
  21. 21.
    Natoli, E.J., Livingston, P.O., Pukel, C.S., et al. (1986) A murine monoclonal antibody detecting N-acetyl-and N-glycolyl-GM2 characterization of cell surface reactivity. Cancer Res. 46:4116–4120.PubMedGoogle Scholar
  22. 22.
    Houghton, A.N., Mintzer, D., Cordon-Cardo, C., et al. (1985) Mouse monoclonal IgG3 antibody detecting GD3 ganlioside: A phase I trial in patients with malignant melanoma. Proc. Natl. Acad. Sci. USA 82:1242–1246.PubMedCrossRefGoogle Scholar
  23. 23.
    Vadhan-Raj, S., Cordon-Cardo, C., Carswell, E., Mintzer, D., Dantis, L., Duteau, C., Templeton, M.A., Oettgen, H.F., Old, L.J., Houghton, A.N. (1988) Phase I trial of a mouse monoclonal antibody against GD3 ganglioside in patients with melanoma: Induction of inflammatory responses at tumor sites. J. Clin. Oncol. 6:1636–1648.PubMedGoogle Scholar
  24. 24.
    Cheung, N.K., Lazarus, H., Miraldi, F.D., Abramowsky, C., Kallick, S., Saaringen, U.M., Spitzer, T., Strandjord, S.E., Coccia, P.F., Berger, N.A. (1987) Ganglioside GD2 specific monoclonal antibody 3F8: A phase I study in patients with neuroblastoma and malignant melanoma. J. Clin. Oncol. 5:1430–1440.PubMedGoogle Scholar
  25. 25.
    Irie, R.F., Morton, D.L. (1986) Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2. Proc. Natl. Acad. Sci. USA 83:8694–8698.PubMedCrossRefGoogle Scholar
  26. 26.
    Oldham, R.K., Foon, K.A., Morgan, C., et al. (1984) Monoclonal antibody therapy of malignant melanoma: In vivo localization in cutaneous metastases after intravenous injection. J. Clin. Oncol. 2:1235–1244.PubMedGoogle Scholar
  27. 27.
    Goodman, G.E., Beaumier, P., Hellstrom, I., et al. (1985) Pilot trial of murine monoclonal antibodies in patients with advanced melanoma. J. Clin. Oncol. 3:340–352.PubMedGoogle Scholar
  28. 28.
    Schroff, R.W., Woodhouse, C.S., Foon, K.A., Oldham, R.K., Farrell, M.M., Klein, R.A., Morgan, A.C. (1985) Intratumor localization of monoclonal antibody with melanoma treated with antibody to a 250000-Dalton melanoma-associated antigen. J. Natl. Cancer Inst. 74:299–306.PubMedGoogle Scholar
  29. 29.
    Hersey, P. (1989) Preclinical and phase I studies of monoclonal antibodies in melanoma. Application to boron neutron capture therapy of melanoma. Pigment Cell Res. 2:264–272.PubMedCrossRefGoogle Scholar
  30. 30.
    Hersey, P., Schibeci, S., Townsend, P., Burns, C., Cheresh, D. (1986) Potentiation of lymphocyte responses by monoclonal antibodies to the ganglioside GD3. Cancer Res. 46:6083–6090.PubMedGoogle Scholar
  31. 31.
    Hersey, P., MacDonald, M., Burns, C., Cheresh, D.A. (1987) Enhancement of cytotoxic and proliferative responses of lymphocytes from melanoma patients by incubation with monoclonal antibodies against ganglioside GD3. Cancer Immunol. Immunother. 24: 144–150.PubMedCrossRefGoogle Scholar
  32. 32.
    Weite, K., Miller, G., Chapman, P.B., et al. (1987) Stimulation of T lymphocyte proliferation by monoclonal antibodies against GD3 ganglioside. J. Immunol. 139:1763–1771.Google Scholar
  33. 33.
    Tai, T., Cahan, L.D., Tsuchida, T., Saxton, R.E., Irie, R.F., Morton, D.L. (1985) Immunogenicity of melanoma-associated gangliosides in cancer patients. Int. J. Cancer 35:607–612.PubMedCrossRefGoogle Scholar
  34. 34.
    Cahan, L.D., Irie, R.F., Singh, R., Cassidenti, A., Paulson, J.C. (1982) Identification of a human neuroectodermal tumor antigen (OFA-1-2) as ganglioside GD2. Proc. Natl. Acad. Sci. USA 79:7629–7633.PubMedCrossRefGoogle Scholar
  35. 35.
    Watanabe, T., Pukel, C.S., Takeyama, H., Lloyd, K.O., Shiku, H., Li, L.T.C., Travassos, L.R., Oettgen, H.F., Old, L.J. (1982) Human melanoma antigen AH is an autoantigenic ganglioside related to GD2. J. Exp. Med. 156:1884–1889.PubMedCrossRefGoogle Scholar
  36. 36.
    Jones, P.C., Sze, L.L., Lim, P.Y., Morton, D.L., Irie, R.F. (1981) Prolonged survival for melanoma patients with elevated IgM antibody to oncofetal antigen. J. Natl. Cancer Inst. 66:249–254.PubMedGoogle Scholar
  37. 37.
    Portoukalian, J., Carrie, S., Dore, J.F., Rumke, P. (1989) Pilot study of immunotherapy with melanoma associated gangliosides in high-risk melanoma patients. In: 2nd Int. Conf. on Melanoma, abstract, p. 322.Google Scholar
  38. 38.
    Hersey, P., Jamal, O., Henderson, C., et al, (1988) Expression of the gangliosides GM3, GD3 and GD2 in tissue sections of normal skin, naevi, primary and metastatic melanoma. Int. J. Cancer 41:336–343.PubMedCrossRefGoogle Scholar
  39. 39.
    Herlyn, M., Thurin, J., Balaban, G., Bennicelli, J.L., Herlyn, D., Elder, D.E., Bondi, E., Guerry, D., Nowell, P., Clark, W.H., Koprowski, H. (1985) Characteristics of cultured human melanocytes isolated from different stages of tumor progression. Cancer Res. 45: 5670–5676.PubMedGoogle Scholar
  40. 40.
    Rosenberg, J.M., Sander, D.J., Derango, R.E., Cheresh, D.A. (1988) Enzymatic basis for increased expression of GD3 on human melanoma cells derived from metastatic lesions. J. Clin. Lab. Anal. 2:91–100.CrossRefGoogle Scholar
  41. 41.
    Goodman, G.E., Hellstrom, I., Hummel, D., Brodzinsky, L., Yeh, M.Y., Hellstrom, K.E. (1987) Proc. Am. Soc. Clin. Oncol. 6:A823.Google Scholar
  42. 42.
    Bajorin, D., Chapman, P., Kunicka, J., Cordon-Carlo, C., Weite, K., Mertelsmann, R., Melamed, M., Oettgen, H.F., Old, L.J., Houghton, A.N. (1987) Phase I trial of a combination of R24 mouse monoclonal antibody and recombinant interleukin-2 in patients with melanoma. Proc. Am. Soc. Clin. Oncol. 6:A827.Google Scholar
  43. 43.
    Lichtin, A., Iliopoulos, D., Guerry, D., Elder, D., Herlyn, D., Steplewski, Z. (1988) Therapy of melanoma with an antimelanoma ganglioside monoclonal antibody: A possible mechanism of a complete response (meeting abstract). In: Proc. Ann. Meet. Am. Soc. Clin. Oncol., Vol. 7, abstract, p. 958.Google Scholar
  44. 44.
    Hersey, P., Jamal, O. (1989) Expression of the gangliosides GD3 and GD2 on lymphocytes in tissue sections of melanoma. Pathology 21:51–58.PubMedCrossRefGoogle Scholar
  45. 45.
    Cantrell, D.A., Smith, K.A. (1983) Transient expression of interleukin 2 receptors. Consequences for T cell growth. J. Exp. Med. 158:1895–1911.PubMedCrossRefGoogle Scholar
  46. 46.
    Smith, K.A. (1984) The interleukin 2 hormone-receptor system. Lymphokine Res. 3:75.Google Scholar
  47. 47.
    Schibeci, S., Hersey, P., Cheresh, D. (1989) Potentiation of interleukin-2 production and its binding by monoclonal antibodies to the gangliosides GD3 and GD2. Cancer Immunol. Immunother. 29:109–117.PubMedCrossRefGoogle Scholar
  48. 48.
    Hersey, P., Schibeci, S., Cheresh, D. (1989) The role of protein kinase C, intracellular calcium levels and cyclic nucleotide levels in augmentation of lymphocyte responses by monoclonal antibodies to GD3 and GD2. Cell. Immunol. 119:263–278.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 1991

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  • Peter Hersey

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