Antibody-Inducing Cancer Vaccines Against Cell-Surface Carbohydrate Antigens

  • Govind Ragupathi
  • John Gathuru
  • Philip O. Livingston
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Carbohydrate cell-surface antigens have proved to be unexpectedly potent targets for immune recognition and attack against cancers (reviewed in 1). Of the many tumorrestricted monoclonal antibodies derived by immunization of mice with human tumor cells, most have been directed against carbohydrate antigens expressed at the cell surface as glycolipids or mucins (2–4). Antibodies against cell-surface antigens such as these are ideally suited for eradication of free tumor cells and micrometastases. This is the role of antibodies against most infectious diseases and it has been accomplished against canc6 r cells as described below in a variety of preclinical models. In adjuvant immunization trials, the primary targets are individual tumor cells or early micrometastases, which may persist for long periods after apparent resection of all residual tumor (5–7). After surgery and completion of chemotherapy is the ideal time for immune intervention, and in particular for administration of cancer vaccines aimed at instructing the immune system to identify and kill these few remaining cancer cells. If antibodies of sufficient titer can be induced against tumor antigens to eliminate tumor cells from the blood and lymphatic systems, and to eradicate micrometastases (making establishment of new metastases no longer possible) this would dramatically change our approach to treating the cancer patient. Aggressive local therapies, including surgery, radiation therapy, and intralesional treatments, might result in long-term control of even metastatic cancers.


Conjugate Vaccine Carbohydrate Antigen Keyhole Limpet Hemocyanine Polysialic Acid General Vaccine 
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  1. 1.
    Livingston PO. Augmenting the immunogenicity of carbohydrate antigens. In: Livingston PO, ed. Cancer vaccines seminars in cancer biology. 1995: 6:357–366.Google Scholar
  2. 2.
    Lloyd KO. Molecular characteristic of tumor antigens. Immunol Allergy Clinics No Am 1990; 10:765–779.Google Scholar
  3. 3.
    Hakomori SI. Tumor-associated carbohydrate antigens. Annu Rev Immunol 1984; 2:103–126.PubMedCrossRefGoogle Scholar
  4. 4.
    Feizi T. Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. Nature 1985; 314:53–57.PubMedCrossRefGoogle Scholar
  5. 5.
    Ghossein R, Scher H, Gerald W, Kelly WK, Curley T, Amsterdam A, Zhang Z-F, Rosai J. Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications. J Clin Oncol 1995; 13:1195–1200.PubMedGoogle Scholar
  6. 6.
    Brossart P, Keilholz U, Willhauck M, Scheibenbogen C, Möhler T, Hunstein W. Hematogenous spread of malignant melanoma cells in different stages of disease. J Investig Dermatol 1993; 101:887–889.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoon DSB, Wang Y, Dale PS, Conrad AJ, Schmid P, Garrison D, Kuo C, Foshag JJ, Nizze AJ, Morton DL. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol 1995; 13:2109–2116.PubMedGoogle Scholar
  8. 8.
    Livingston PO. The case for melanoma vaccines that induce antibodies. In: Kirkwood JM, ed. Molecular diagnosis prevention and treatment of melanoma. New York: Marcel Dekker, 1998:139–157.Google Scholar
  9. 9.
    Zhang H, Zhang S, Cheung NK, Ragupathi G, Livingston PO. Antibodies can eradicate cancer micrometastases. Cancer Res 1998; 58:2844–2849.PubMedGoogle Scholar
  10. 10.
    Jones PC, Sze LL, Liu PY, Morton DL, Irie RF. Prolonged survival for melanoma patients with elevated IgM antibody to oncofetal antigen. J Natl Cancer Inst 1981; 66:249–254.PubMedGoogle Scholar
  11. 11.
    Livingston PO, Ritter G, Srivastava P. Padavan M, Calves MJ, Oettgen HF, Old U. Characterization of IgG and IgM antibodies induced in melanoma patients by immunization with purified GM2 ganglioside. Cancer Res 1989; 49:7045–7050.PubMedGoogle Scholar
  12. 12.
    Livingston PO, Wong GYC, Adluri S, Tao Y, Padavan M, Parente R, Hanlon C, Helling F, Ritter G, Oettgen HF, Old L. Improved survival in AJCC stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 1994; 12:1036–1044.PubMedGoogle Scholar
  13. 13.
    MacLean GD, Reddish MA, Koganty RR, Longenecker BM. Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother 1996; 19:59–68.CrossRefGoogle Scholar
  14. 14.
    Zhang S, Helling F, Lloyd KO, Livingston PO. Increased tumor cell reactivity and complement dependent cytotoxicity with mixtures of monoclonal antibodies against different gangliosides. Cancer Immunol Immunother 1995; 40:88–94.PubMedCrossRefGoogle Scholar
  15. 15.
    Fung PYS, Madej M, Koganty RR, Longenecker BM. Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate. Cancer Res 1990; 50:4308–4314.PubMedGoogle Scholar
  16. 16.
    Singhal A, Fohn M, Hakomori S-I. Induction of a-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice. Cancer Res 1991; 51: 1406–1411.PubMedGoogle Scholar
  17. 17.
    Zhao X-J, Cheung N-K. GD2 Oligosaccharide: target for cytotoxic T lymphocytes. J Exp Med 1995; 182:67–74.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhang S, Cordon-Cardo C, Zhang HS, Reuter VE, Adluri S, Hamilton WB, Lloyd KO, Livingston PO. Selection of carbohydrate tumor antigens as targets for immune attack using immunohistochemistry. I. Focus on gangliosides. Int J Cancer 1997; 73:42–49.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang S, Zhang HS, Cordon-Cardo C, Reuter VE, Singhal AK, Lloyd KO, Livingston PO. Selection of tumor antigens as targets for immune attack using immunohistochemistry. II. Blood group-related antigens. Int J Cancer 1997; 73:50–56.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhang S, Zhang HS, Cordon-Cardo C, Ragupathi G, Livingston PO. Selection of tumor antigens as targets for immune attack using immunohistochemistry: III protein antigens. Clin Cancer Res 1998; 4:2669–2676.PubMedGoogle Scholar
  21. 21.
    Zhang S, Zhang HS, Reuter VE, Lloyd KO, Scher HI, Livingston PO. Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers. Clin Cancer Res 1998; 4:295–302.PubMedGoogle Scholar
  22. 22.
    Nishinaka Y, Ravindranath MH, Irie RF. Development of a human monoclonal antibody to ganglioside GM2 with potential for cancer treatment. Cancer Res 1996; 56:5666–5671.PubMedGoogle Scholar
  23. 23.
    Nakamura K, Koike M, Shitara K, Kuwana Y, Kiuragi K, Igarashi S, Hasegawa M, Hanai N. Chimeric anti-ganglioside GM2 antibody with antitumor activity. Cancer Res 1994; 54:1511–1516.PubMedGoogle Scholar
  24. 24.
    Hellström I, Garrigues HJ, Garrigues U, Hellströrn KE. Highly tumor-reactive, internalizing, mouse monoclonal antibodies to Le-related cell surface antigens. Cancer Res 1990; 50:2183–2190.PubMedGoogle Scholar
  25. 25.
    Canevari S, Fossati G, Balsari A, Sonnino S, Colnaghi MI. Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells. Cancer Res 1983; 43:1301–1305.PubMedGoogle Scholar
  26. 26.
    Mènard S, Tagliabue E, Canevari S, Fossati G, Colnaghi MI. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res 1983; 43:1295–1300.PubMedGoogle Scholar
  27. 27.
    Perrone F, Ménard S, Canevari S, Claabrese M, Boracchi P, Bufalino R, Testori S, Baldini M, Colnaghi MI. Prognostic significance of the CaMBr 1 antigen on breast carcinoma: relevance of the type of recognized glycoconjugate. Eur J Cancer 1993; 29A:2113–2117.CrossRefGoogle Scholar
  28. 28.
    Colnaghi MI, Menard S, Da Dalt JG, Agresti R, Cattoretti G, Andreola S, Di Fronzo G, Del Vecchio M, Verderio L, Cascinelli N, Rilke F. A multiparametric study by monoclonal antibodies in breast cancer. In: Ceriani RL, ed. Immunological approaches to the diagnosis and therapy of breast cancer. New York: Plenum, 1987:21–32.CrossRefGoogle Scholar
  29. 29.
    Trail PA, Willner SJ, Lasch AJ, Henderson S, Hofstead AM, Casazza AM, Firestone RA, Hellstrom I, Hellstrom KE. Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 1993; 261:212–215.PubMedCrossRefGoogle Scholar
  30. 30.
    Burchell J, Taylor-Papadimitriou J, Boshell M, Gendler S, Duhig T. A short sequence, within the amino acid tandem repeat of a cancer-associated mucin, contains immunodominant epitopes. Int J Cancer 1989; 44:691–696.PubMedCrossRefGoogle Scholar
  31. 31.
    Gendler SJ, Spicer AP, Lalani E-N, Duhig T, Peat N, Burchell J, Pemberton L, Boshell M, TaylorPapadimitriou J. Structure and biology of a carcinoma-associated mucin, MUCl. Am Rev Respir Dis 1991; 144:542–547.Google Scholar
  32. 32.
    Perez L, Hayes DF, Maimonis P, Abe M, O’Hara C, Kufe DW. Tumor selective reactivity of a monoclonal antibody prepared against a recombinant peptide derived from the DF3 human breast carcinomaassociated antigen. Cancer Res 1992; 52:2563–2568.Google Scholar
  33. 33.
    Musselli C, Ragupathi G, Gilewski T, Panageas KS, Spinat Y, Livingston PO. Reevaluation of the cellular immune response in breast cancer patients vaccinated with MUC1. Intl J Cancer 2002; 97: 660–667.CrossRefGoogle Scholar
  34. 34.
    Springer GF. T and Tn, general carcinoma autoantigens. Science 1984; 224:1198–1206.PubMedCrossRefGoogle Scholar
  35. 35.
    Lloyd KO. Blood group antigens as markers for normal differentiation and malignant change in human tissues. Amer J Clin Pathol 1987; 87:129–139.Google Scholar
  36. 36.
    Itzkowitz S, Bloom EJ, Kokal, WA, Modin G, Hakomori S-I, Kim YS. Sialosyl Tn: a novel mucin antigen associated with prognosis in colorectal carcinoma patients. Cancer 1990; 66:1960–1966.PubMedCrossRefGoogle Scholar
  37. 37.
    Cho S-H, Sahin A, Hortobagyi GN, Hittelman WN, Dhingra K. Sialyl-Tn antigen expression occurs early during human mammary carcinogenesis and is associated with high nuclear grade and aneuploidy. Cancer Res 1994; 54:6302–6305.PubMedGoogle Scholar
  38. 38.
    Thor A, Obuchi N, Szpak CA, Johnston WW, Schlom J. Distribution of oncofetal antigen tumorassociated glycoprotein-72 defined by monoclonal antibody B72.3. Cancer Res 1986; 46:3118–3124.PubMedGoogle Scholar
  39. 39.
    Longenecker BM, Willans DJ, MacLean GD, Suresh S, Noujaim AA. Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of the expression of Thomsen-Friedenreichlike and Tn-like antigens on human cancers. J Natl Cancer Inst 1987; 78:489–496.PubMedGoogle Scholar
  40. 40.
    Contegiacomo A, Alimandi M, Muraro R, Pizzi C, Calderopoli R, De Marchis L, Sgambato A, Pettinato G, Petrella G, De Filippo MR, et al. Expression of epitopes of the tumor-associated glycoprotein 72 and clinicopathological correlations in mammary carcinomas. Eur J Cancer 1994; 30A:813–820.CrossRefGoogle Scholar
  41. 41.
    Zhang S, Walberg LA, Ogata S, Itzkowitz SH, Koganty RR, Reddish M, Gandhi SS, Longenecker BM, Lloyd KO, Livingston PO. Immune sera and monoclonal antibodies define two configurations for the sialyl Tn tumor antigen. Cancer Res 1995; 55:3364–3368.PubMedGoogle Scholar
  42. 42.
    Kostakoglu L, Divgi CR, Gilewski T, Theodoulou M, Schlom J, Larson SM. Phase II radioimmunotherapy (RIT) trial with 1–131 labeled monoclonal antibody CC49 in Tag-72 expressing breast cancer. J Nucl Med 1994; 35(Suppl):234.Google Scholar
  43. 43.
    Larson SM, Carrasquillo JA, Colcher DC, Yokoyama K, Reynolds JC, Bacharach SA, Raubitchek A, Pace L, Finn RD, Rotman M. Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatosis. J Nucl Med 1991; 32:1661–1667.PubMedGoogle Scholar
  44. 44.
    MacLean GD, McEwan A, Noujaim AA, Sykes TR, Suresh MR, Catz Z, Hooper HR, Longenecker BM. A novel strategy for cancer immunoscinitgrapy. Antibody Immunoconj Radiopharmaceut 1989; 2:15.Google Scholar
  45. 45.
    Itzkowitz SH, Yuan M, Montgomery CK, Kjeldsen T, Takahashi HK, Bigbee WK, Kim YS. Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res 1989; 49:197–204.PubMedGoogle Scholar
  46. 46.
    MacLean GD, Reddish MA, Bowen-Yacyshyn MB, Poppema S, Longenecker BM. Active specific immunotherapy against adenocarcinomas. Cancer Invest 1994; 12:46–56.PubMedCrossRefGoogle Scholar
  47. 47.
    Fung PYS, Madej M, Koganty RR, Longenecker BM. Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate. Cancer Res 1990; 50:4308–4314.PubMedGoogle Scholar
  48. 48.
    Lackie PM, Zuber C, Roth J. Polysialic acid of the neural cell adhesion molecule (N-CAM) is widely expressed during organogenesis in mesodermal and endodermal derivatives. Differentiation 1994; 57:119–131.PubMedCrossRefGoogle Scholar
  49. 49.
    Komminoth P, Roth J, Lackie PM, Bitter-Suermann D, Heintz PU. Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. Am J Pathol 1991; 139:297–304.PubMedGoogle Scholar
  50. 50.
    Hayrinen J, Jennings H, Raff HV, Rougon G, Hanai N, CGerardy-Schahn K, J. Antibodies to polysialic acid and its N-propyl derivative: binding properties and interaction with human embryonal brain glycopeptides. J Infect Dis 1995; 171:1481–1490.PubMedCrossRefGoogle Scholar
  51. 51.
    MacLean GD, Reddish M, Koganty RR, Wong T, Gandhi S, Smolenski M, Samuel J, Nabholtz JM, Longenecker BM. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. Cancer Immunol Immunother 1993; 36:215–222.PubMedCrossRefGoogle Scholar
  52. 52.
    Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T cell recognition: molecular mechanisms and functional significance. Adv Immunol 2000; 74:181–273.PubMedCrossRefGoogle Scholar
  53. 53.
    Ferrone, S. Tumor escape mechanisms. Seminars Cancer Biol 2002;12:1–86.CrossRefGoogle Scholar
  54. 54.
    Gottlinger HG, Funke I, Johnson JP, Gokel JM, Riethmuller G. The epithelial cell surface antigen 171A, a target for antibody-mediated tumor therapy: its biochemical nature, tissue distribution and recognition by different monoclonal antibodies. Int J Cancer 1986; 38:47–53.PubMedCrossRefGoogle Scholar
  55. 55.
    Szala S, Froehlich M, Scollon M, Kasai Y, Steplewski Z, Koprowski H, Linnenbach AJ. Molecular cloning of cDNA for the carcinoma associated antigen GA733.2. Proc Natl Acad Sci USA 1990; 87:3542–3546.PubMedCrossRefGoogle Scholar
  56. 56.
    LoBuglio AF, Saleh MN, Lee J, Khazaeli MB, Carrano R, Holden H, Wheeler R. Phase I trial of multiple large doses of murine monoclonal antibody C017–1A. I. Clinical aspects. J Nat. Cancer Inst 1988; 80:932–936.PubMedCrossRefGoogle Scholar
  57. 57.
    Riethmuller G, Schneider-Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J, The German Cancer Aid 17–1A Study Group. Randomized trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. Lancet 1994; 343:1177–1183.PubMedCrossRefGoogle Scholar
  58. 58.
    Somasundaram R, Zaloudik J, Jacob L, Benden A, Sperlagh M, Hart E, Marks G, Kane M, Mastrangelo M, Herlyn D. Induction of antigen-specific T and B cell immunity in colon carcinoma patients by antiidiotypic antibody. J Immunol 1995; 155:3253–3261.PubMedGoogle Scholar
  59. 59.
    Yin WT, Dnistrian A, Lloyd KO. Ovarian cancer antigen CA125 is encoded by the MUC 16 mum gene. Intl J Cancer 2002; 98:737–740.CrossRefGoogle Scholar
  60. 60.
    Zhang S, Graeber LA, Helling F, Ragupathi G, Adluri S, Lloyd KO, Livingston PO. Augmenting the immunoaenicitv of synthetic MUC1 peptide vaccines in mice. Cancer Res 1996; 56:3315–3319.PubMedGoogle Scholar
  61. 61.
    Livingston PO, Zhang S, Walberg L, Ragupathi G, Helling F, Fleischer M. Tumor cell reactivity mediated by IgM antibodies in sera from melanoma patients vaccinated with GM2-KLH is increased by IgG antibodies. Cancer Immunol Immunother 1997; 43:324–330.PubMedCrossRefGoogle Scholar
  62. 62.
    Livingston PO, Calves MJ, Natoli Jr EJ. Approaches to augmenting the immunogenicity of the ganglioside GM2 in mice: purified GM2 is superior to whole cells. J Immunol 1987; 138:1524–1529.PubMedGoogle Scholar
  63. 63.
    Helling F, Zhang A, Shang A, Adluri S, Calves M, Koganty RR, Longenecker BM, Oettgen HF, Livingston PO. GM2-KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. Cancer Res 1995; 55:2783–2788.PubMedGoogle Scholar
  64. 64.
    Livingston PO, Adluri S, Helling F, Yao T-J, Kensil CR, Newman MJ, Marciani, D. Phase I trial of immunological adjuvant QS-21 with a GM2 ganglioside-KLH conjugate vaccine in patients with malignant melanoma. Vaccine 1994; 12:1275–1280.PubMedCrossRefGoogle Scholar
  65. 65.
    Kim S-K, Ragupathi G, Cappello S, Kagan E, Livingston PO. Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates. Vaccine 2000; 19:530–537.PubMedCrossRefGoogle Scholar
  66. 66.
    Ritter G, Boosfeld E, Markstein E, Yu RK, Ren S, Oettgen HF, Old LJ, Livingston PO. Biochemical and serological characteristics of natural 9–0-acetyl GD3 from human melanoma and bovine buttermilk and chemically 0-acetylated GD3. Cancer Res 1990; 50:1403–1410.PubMedGoogle Scholar
  67. 67.
    Ritter G, Boosfeld E, Calves MJ, Oettgen HF, Old LJ, Livingston PO. Antibody response after immunization with gangliosides GD3, GD3 lactones, GD3 amide and GD3 gangliosidol in the mouse. GD3 lactone I induces antibodies reactive with human melanoma. Immunobiol 1990; 182:32–43.CrossRefGoogle Scholar
  68. 68.
    Ritter G, Boosfeld E, Adluri R, Calves M, Oettgen HF, Old LJ, Livingston PO. Antibody response to immunization with ganglioside GD3 and GD3 congeners (lactones, amide and gangliosidol) in patients with malignant melanoma. Int J Cancer 1991; 48:379–385.PubMedCrossRefGoogle Scholar
  69. 69.
    Ritter G, Ritter-Boosfeld E, Adluri R, Calves M, Ren S, Yu RK, Oettgen HF, Old LJ, Livingston PO. Analysis of the antibody response to immunization with purified 0-acetyl GD3 gangliosides in patients with malignant melanoma. Int J Cancer 1995; 62:1–5.CrossRefGoogle Scholar
  70. 70.
    Helling F, Shang A, Calves M, Zhang S, Ren S, Yu RK, Oettgen HF, Livingston PO. GD3 vaccines for melanoma: superior immunogenicity of keyhole limpet hemocyanin conjugate vaccines. Cancer Res 1994; 54:197–203.PubMedGoogle Scholar
  71. 71.
    Kensil CR, Patel U, Lennick M, Marciani D. Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. J Immunol 1982; 12:91–96.Google Scholar
  72. 72.
    Livingston PO, Natoli Jr EJ, Calves M, Stockert E, Oettgen HF, Old L. Vaccines containing purified GM2 ganglioside elicit GM2 antibodies in melanoma patients. Proc Natl Acad Sci USA 1987; 84:2911’2915.PubMedCrossRefGoogle Scholar
  73. 73.
    Kirkwood J, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, Rao U. High-dose interferon Alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E16954/ S9512/C50901. J Clin Immuno 2001; 19:2370–2380.Google Scholar
  74. 74.
    Dickler MN, Ragupathi G, Liu NX, Musselli C, Martino DJ, Miller VA, Kris MG, Brezicka FT, Livingston PO, Grant SC. Immunogenicity of the fucosyl-GM1-keyhole limpet hemocyanin (KLH) conjugate vaccine in patients with small cell lung cancer. Cancer Res 1999; 5:2773–2779.Google Scholar
  75. 75.
    Nores GA, Dohi T, Taniguchi M, Hakomori SI. Density-dependent recognition of cell surface GM3 by a certain anti-melanoma antibody, and GM3 lactone as a possible immunogen. J Immunol 1987; 139:3171.PubMedGoogle Scholar
  76. 76.
    Bilodeau MT, Park TK, Hu S, Tandolph JT, Danishefsky SJ, Livingston PO, Zhang S. Total synthesis of a human breast tumor associated antigen. J Amer Chem Soc 1995; 117:7840–7841.CrossRefGoogle Scholar
  77. 77.
    Ragupathi G, Park TK, Zhang S, Kim IJ, Graeber K, Adluri S, Lloyd KO, Danishefsky SJ, Livingston PO. Immunization of mice with the synthetic hexasaccharide Globo H results in antibodies against human cancer cells. Angew Chem Int Ed Engl 1997; 36:125–128.CrossRefGoogle Scholar
  78. 78.
    Behar V, Danishefsky SJ. A highly convergent synthesis of the Lewis-Y blood group determinant in conJugatable form. Angew Chem Int Ed Engl 1994; 33:1468–1470.CrossRefGoogle Scholar
  79. 79.
    Ragupathi G, Slovin SF, Adluri S, Sames D, Kim I-J, Kim HM, Spassova M, Bornmann WG, Lloyd KO, Scher HI, Livingston PO, Danishefsky SJ. A fully synthetic globo H carbohydrate vaccine induces a focused humoral response in prostate cancer patients: a proof of principle. Angew Chem Intl Ed Engl 1999; 38:563–566.CrossRefGoogle Scholar
  80. 80.
    Kudryashov V, Kim HM, Ragupathi G, Danishefsky SJ, Livingston PO, Lloyd KO. Immunogenicity of synthetic conjugates of Lewisy oligosaccharide with protein in mice: towards the design of anticancer vaccines. Cancer Immunol Immunother 1998; 45:281–286.PubMedCrossRefGoogle Scholar
  81. 81.
    Slovin SF, Ragupathi G, Adluri S, Ungers G, Terry K, Kim S, Spassova M, Bornmann, WG, Fazzari M, Dantis L, Olkiewicz K, Lloyd KO, Livingston PO, Danishefsky SJ, Scher HI. Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic Globo H hexasaccharide conjugate in man. Proc Natl Acad Sci USA 1999; 96:5710–5715.PubMedCrossRefGoogle Scholar
  82. 82.
    Sabbatini P, Kudryashov V, Ragupathi G, Danishefsky S, Livingston PO, Bornmann W, Spassova M, Zatorski A, Spriggs D, Aghajanian C, Soignet S, Peyton M, O’Flaherty C, Curtin J, Lloyd KO. Immunization of ovarian cancer patients with a synthetic LewisY-protein conjugate vaccine: a phase 1 trial. Int J Cancer 2000; 87:79–85.PubMedCrossRefGoogle Scholar
  83. 83.
    Gilewski T, Ragupathi G, Bhuta S, Williams LJ, Musselli C, Zhang XF, Bencsath KP, Panageas KS, Chin J, Norton L, Houghton AN, Livingston PO, Danishefsky SJ. Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial. Proc Natl Acad Sci USA 2001; 98:3270–3275.PubMedCrossRefGoogle Scholar
  84. 84.
    Adluri S, Helling F, Calves MT, Lloyd KO, Livingston PO. Immunogenicity of synthetic TF- and sTnKLH conjugates in colorectal carcinoma patients. Cancer Immunol Immunother 1995; 41:185–192.PubMedCrossRefGoogle Scholar
  85. 85.
    MacLean GD, Bowen-Yacyshyn MB, Samuel J, Meikle A, Stuart G, Nation J, Poppema S, Jerry M, Koganty RR, Wong T, Longenecker BM. Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen. J Immunother 1992; 11:292–305.PubMedCrossRefGoogle Scholar
  86. 86.
    Livingston PO, Koganty RR, Longenecker BM, Lloyd KO, Calves M. Studies on the immunogenicity of synthetic and natural Thomsen-Friedenreich (TF) antigens in mice: augmentation of the response by Quil A and SAF-m adjuvants and analysis of the specificity of the responses. Vaccine Res 1992; 1: 99–109.Google Scholar
  87. 87.
    Nakada H, Inoue M, Numata Y, Tanaka N, Funakoshi I, Fukui S, Mellors A, Yamashina I. Epitopic structure of Tn glycophorin A for an anti-Tn antibody (MLS 128). Proc Nat. Acad Sci USA 1993; 90:2495–2499.PubMedCrossRefGoogle Scholar
  88. 88.
    Kurosaka A, Kitagawa H, Fukui S, Numata Y, Nakada H, Funakoshi I, Kawasaki T, Ogawa T, Iijima H, Yamashina I. A monoclonal antibody that recognizes a cluster of a disaccharide, NeuAca2–6Ga1NAc, in mucin-type glycoproteins. J Biol Chem 1988; 263:8724–8726.PubMedGoogle Scholar
  89. 89.
    Springer GF, Desai PR, Tegtmeyer H, Spencer BD, Scanlon EF. Pancarcinoma T/Tn antigen detects human carcinoma long before biopsy does and its vaccine prevents breast carcinoma recurrence. Ann NY Acad Sci 1993; 690:355–357.PubMedCrossRefGoogle Scholar
  90. 90.
    Springer, GF. Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J Mol Med 1997; 75:594–602.PubMedCrossRefGoogle Scholar
  91. 91.
    MacLean GD, Miles DW, Rubens RD, Reddish MA, Longenecker BM. Enhancing the effect of Theratope STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J Immunother 1996;19:309–316.CrossRefGoogle Scholar
  92. 92.
    Pon RA, Lussier M, Yang Q-L, Jennings HJ. N-Propionylated group B meningococcal polysaccharide mimics a unique bactericidal capsular epitope in group B Neisseria menigitidis. J Exp Med 1997; 185: 1929–1938.PubMedCrossRefGoogle Scholar
  93. 93.
    Colten HR, Rosen FS. Complement deficiencies. Ann Rev Immunol 1992; 10:809–834.CrossRefGoogle Scholar
  94. 94.
    Ragupathi G, Meyers M, Adluri S, Howard L, Musselli C, Livingston PO. Induction of antibodies against GD3 ganglioside in melanoma patients by vaccination with GD3-lactone-KLH conjugate plus immunological adjuvant QS-21. Int J Cancer 2000;85:659–666.PubMedCrossRefGoogle Scholar

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© Humana Press Inc. 2004

Authors and Affiliations

  • Govind Ragupathi
  • John Gathuru
  • Philip O. Livingston

There are no affiliations available

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