Advertisement

Analysis of Humoral Immune Responses in Vaccine Trials

  • Rajasekharan Somasundaram
  • Tianqian Zhang
  • Dorothee Herlyn
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

It has been widely recognized that both cell-mediated and humoral immunity play important roles in the inhibition of tumor growth in vaccinated cancer patients. This chapter will only briefly summarize available data that emphasize a role of cellular immunity, including proliferating, cytokine-secreting, cytolytic and/or delayed-type hypersensitive (DTH) T lymphocytes, in the control of tumor growth. We will elaborate on why T lymphocytes often are ineffective against tumors, emphasizing the important role of humoral immunity in cancer growth control. This role has recently been highlighted by the approval of monoclonal antibody (MAb) treatments for cancer patients by the Food and Drug Administration (FDA). However, the biological half-life of MAbs is short, rendering the induction of long-lasting active specific humoral immunity by vaccines a highly attractive alternative. Studies in animals have demonstrated a positive correlation between the induction of antibody responses following vaccination and tumor regression. Similarly, a correlation between humoral immune response induction and beneficial clinical responses has been demonstrated in cancer patients. Since vaccine- induced antibodies must bind to the tumor cell surface in order to destroy tumor cells in conjunction with effector cells or complement, emphasis is placed on those studies that have demonstrated the induction of tumor cell-binding antibodies by vaccines in cancer patients. The vast majority of studies have demonstrated binding of the elicited antibodies to proteins only and are only summarized here.

Keywords

Chronic Lymphocytic Leukemia Melanoma Patient Humoral Immune Response Gemtuzumab Ozogamicin Tumor Cell Surface 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Wang F, Bade E, Kuniyoshi C, Spears L, Jeffery G, Marty V, Groshen S, Weber J. Phase I trial of a MART-1 peptide vaccine with incomplete Freund’s adjuvant for resected high-risk melanoma. Clin Cancer Res 1999; 5:2756–2765.PubMedGoogle Scholar
  2. 2.
    Kwak LW, Campbell MJ, Czerwinski DK, Hart S, Miller RA, Levy R. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N Engl J Med 1992; 327:1209–1215.PubMedCrossRefGoogle Scholar
  3. 3.
    Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML. Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. Cancer Res 2000; 60:829–833.PubMedGoogle Scholar
  4. 4.
    Fong L, Brockstedt D, Benike C, Breen JK, Strang G, Ruegg CL, Engleman EG. Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J Immunol 2001; 167:7150–7156.PubMedGoogle Scholar
  5. 5.
    Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, Davis MM, Engleman EG. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 2001; 98:8809–8814.PubMedCrossRefGoogle Scholar
  6. 6.
    Mitchell MS, Kan-Mitchell J, Kempf RA, Harel W, Shau HY, Lind S. Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res 1988; 48:5883–5893.PubMedGoogle Scholar
  7. 7.
    Hsueh EC, Gupta RK, Qi K, Morton DL. Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine. J Clin Oncol 1998; 16:2913–2920.PubMedGoogle Scholar
  8. 8.
    Barth A, Hoon DS, Foshag LJ, Nizze JA, Famatiga E, Okun E, Morton DL. Polyvalent melanoma cell vaccine induces delayed-type hypersensitivity and in vitro cellular immune response. Cancer Res 1994; 54:3342–3345.PubMedGoogle Scholar
  9. 9.
    Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA, Pennington R, Watson TM, Reynolds CW, Gause BL, Duffey PL, Jaffe ES, Creekmore SP, Longo DL, Kwak LW. Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med 1999; 5:1171–1177.PubMedCrossRefGoogle Scholar
  10. 10.
    Nelson EL, Li X, Hsu FJ, Kwak LW, Levy R, Clayberger C, Krensky AM. Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin’s lymphoma. Blood 1996; 88:580–589.PubMedGoogle Scholar
  11. 11.
    Bystryn JC, Oratz R, Roses D, Harris M, Henn M, Lew R. Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage II malignant melanoma. Cancer 1992; 69:1157–1164.PubMedCrossRefGoogle Scholar
  12. 12.
    Morton DL, Foshag LJ, Hoon DS, Nizze JA, Famatiga E, Wanek LA, Chang C, Davtyan DG, Gupta RK, Elashoff R, Irie RF. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg 1992; 216:463–482.PubMedCrossRefGoogle Scholar
  13. 13.
    Berd D, Maguire HC, Jr, Schuchter LM, Hamilton R, Hauck WW, Sato T, Mastrangelo MJ. Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment after resection of nodal metastases. J Clin Oncol 1997; 15:2359–2370.PubMedGoogle Scholar
  14. 14.
    Berd D, Sato T, Mastrangelo MJ. Effect of the dose and composition of an autologous hapten-modified melanoma vaccine on the development of delayed-type hypersensitivity responses. Cancer Immunol Immunother 2002; 51:320–326.PubMedCrossRefGoogle Scholar
  15. 15.
    Hicklin DJ, Marincola FM, Ferrone S. HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today 1999; 5:178–186.PubMedCrossRefGoogle Scholar
  16. 16.
    Cerwenka A, Lanier LL. Natural killer cells, viruses and cancer. Nat Rev Immunol 2001; 1:41–49.PubMedCrossRefGoogle Scholar
  17. 17.
    Yang G, Hellström KE, Hellström I, Chen L. Antitumor immunity elicited by tumor cells transfected with B7–2, a second ligand for CD28/CTLA-4 costimulatory molecules. J Immunol 1995; 154:2794–2800.PubMedGoogle Scholar
  18. 18.
    Yang G, Mizuno MT, Hellström KE, Chen L. B7-negative versus B7-positive P815 tumor. J Immunol 1997; 158:851–858.PubMedGoogle Scholar
  19. 19.
    Levy LS, Bost KL. Mechanisms that contribute to the development of lymphoid malignancies: roles for genetic alterations and cytokine production. Crit Rev Immunol 1996; 16:31–57.PubMedCrossRefGoogle Scholar
  20. 20.
    Gimmi CD, Morrison BW, Mainprice BA, Gribben JG, Boussiotis VA, Freeman GJ, Park SY, Watanabe M, Gong J, Hayes DF, Kufe DW, Nadler LM. Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells. Nat Med 1996; 2:1367–1370.PubMedCrossRefGoogle Scholar
  21. 21.
    Nakashima M, Sonoda K, Watanabe T. Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nat Med 1999; 5:938–942.PubMedCrossRefGoogle Scholar
  22. 22.
    Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 1998; 396:699–703.PubMedCrossRefGoogle Scholar
  23. 23.
    Walker PR, Saas P, Dietrich PY. Tumor expression of Fas ligand (CD95L) and the consequences. Curr Opin Immunol 1998; 10:564–572.PubMedCrossRefGoogle Scholar
  24. 24.
    Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8:793–800.PubMedGoogle Scholar
  25. 25.
    Finke JH, Zea AH, Stanley J, Longo DL, Mizoguchi H, Tubbs RR, Wiltrout RH, O’Shea JJ, Kudoh S, Klein E, Bukowski RM, Ochoa AC. Loss of T-cell receptor zeta chain and p561ck in T-cells infiltrating human renal cell carcinoma. Cancer Res 1993; 53:5613–5616.PubMedGoogle Scholar
  26. 26.
    Healy CG, Simons JW, Carducci MA, DeWeese TL, Bartkowski M, Tong KP, Bolton WE. Impaired expression and function of signal-transducing zeta chains in peripheral T cells and natural killer cells in patients with prostate cancer. Cytometry 1998; 32:109–119.PubMedCrossRefGoogle Scholar
  27. 27.
    Mizoguchi H, O’Shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 1992; 258:1795–1798.PubMedCrossRefGoogle Scholar
  28. 28.
    Levey DL, Srivastava PK. T cells from late tumor-bearing mice express normal levels of p561ck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity. J Exp Med 1995; 182:1029–1036.PubMedCrossRefGoogle Scholar
  29. 29.
    Salvadori S, Gansbacher B, Pizzimenti AM, Zier KS. Abnormal signal transduction by T cells of mice with parental tumors is not seen in mice bearing IL-2-secreting tumors. J Immunol 1994; 153:5176–5182.PubMedGoogle Scholar
  30. 30.
    Wang Q, Stanley J, Kudoh S, Myles J, Kolenko V, Yi T, Tubbs R, Bukowski R, Finke J. T cells infiltrating non-Hodgkin’ s B cell lymphomas show altered tyrosine phosphorylation pattern even though T cell receptor/CD3-associated kinases are present. J Immunol 1995; 155:1382–1392.PubMedGoogle Scholar
  31. 31.
    Somasundaram R, Jacob L, Swoboda R, Caputo L, Song H, Basak S, Monos D, Peritt D, Marincola F, Cai D, Birebent B, Bloome E, Kim J, Berencsi K, Mastrangelo M, Herlyn D. Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-ß31. Cancer Res 2002; 62:5267–5272.PubMedGoogle Scholar
  32. 32.
    McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, BenceBruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998; 16:2825–2833.PubMedGoogle Scholar
  33. 33.
    Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpressed HER2. N Engl J Med 2001; 344:783–792.PubMedCrossRefGoogle Scholar
  34. 34.
    Sievers EL, Appelbaum FR, Spielberger RT, Forman SJ, Flowers D, Smith FO, Shannon-Dorcy K, Berger MS, Bernstein ID. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 1999; 93:3678–3684.PubMedGoogle Scholar
  35. 35.
    Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, Karanes C, Theobald M, Bennnett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR, Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33positive acute myeloid leukemia in first relapse. J Clin Oncol 2001; 19:3244–3254.PubMedGoogle Scholar
  36. 36.
    Lundin J, Kimby E, Björkholm M, Broliden P-A, Celsing F, Hjalmar V, Möllgård L, Rebello P, Hale G, Waldmann H, Mellstedt H, Österborg A. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002; 100:768–773.PubMedCrossRefGoogle Scholar
  37. 37.
    Osterborg A, Dyer MJ, Bunjes D, Pangalis GA, Bastion Y, Catovsky D, Mellstedt H. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European study group of CAMPATH-1H treatment in chronic lymphocytic leukemia. J Clin Oncol 1997; 15:1567–1574.PubMedGoogle Scholar
  38. 38.
    Maloney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance. Semin Oncol 2002; 29:2–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 2000; 6:443–446.PubMedCrossRefGoogle Scholar
  40. 40.
    Linenberger ML, Hong T, Flowers D, Sievers EL, Gooley TA, Bennett JM, Berger MS, Leopold LH, Appelbaum FR, Bernstein ID. Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin. Blood 2001; 98:988–994.PubMedCrossRefGoogle Scholar
  41. 41.
    Sears HF, Mattis J, Herlyn D, Häyry P, Atkinson B, Ernst C, Steplewski Z, Koprowski H. Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours. Lancet 1982; 1:762–765.PubMedCrossRefGoogle Scholar
  42. 42.
    Meredith RF, LoBuglio AF, Plott WE, On RA, Brezovich IA, Russell CD, Harvey EB, Yester MV, Wagner AJ, Spencer SA, Wheeler RH, Saleh MN, Rogers KJ, Polansky A, Salter MM, Khazaeli MB. Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG 1 ,k 17–1A monoclonal antibody. J Nucl Med 1991; 32:1162–1168.PubMedGoogle Scholar
  43. 43.
    Herbst RS, Kim ES, Harari PM. IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer. Expert Opin Biol Ther 2001; 1:719–732.PubMedCrossRefGoogle Scholar
  44. 44.
    Scott AM, Lee FT, Hopkins W, et al. Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial. J Clin Oncol 2001; 19:3976–3987.PubMedGoogle Scholar
  45. 45.
    Harada M, Pearson G, Redmon L, Winters E, Kasuga S. Antibody production and interaction with lymphoid cells in relation to tumor immunity in the Moloney sarcoma virus system. J Immunol 1975; 114:1318–1322.PubMedGoogle Scholar
  46. 46.
    Slauson DO, Osburn BI, Shifrine M, Dungworth DL. Regression of feline sarcoma virus-induced sarcomas in dogs. II. Immunologic investigations. J Natl Cancer Inst 1975; 54:371–377.PubMedGoogle Scholar
  47. 47.
    Herlyn D, Somasundaram R, Li W, Maruyama H. Anti-idiotype cancer vaccines: past and future. Cancer Immunol Immunother 1996; 43:65–76.PubMedCrossRefGoogle Scholar
  48. 48.
    Wikstrand CJ, Cole VR, Crotty LE, Sampson JH, Bigner DD. Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system. Cancer Immunol Immunother 2002; 50:639–652.PubMedCrossRefGoogle Scholar
  49. 49.
    Rosales C, Graham VV, Rosas GA, Merchant H, Rosales R. A recombinant vaccinia virus containing the papilloma E2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity. Cancer Immunol Immunother 2000; 49:347–360.PubMedCrossRefGoogle Scholar
  50. 50.
    Ravindranath MH, Kelley MC, Jones RC, Amiri AA, Bauer PM, Morton DL. Ratio of IgG:IgM antibodies to sialyl Lewis(x) and GM3 correlates with tumor growth after immunization with melanoma-cell vaccine with different adjuvants in mice. Int J Cancer 1998; 75:117–124.PubMedCrossRefGoogle Scholar
  51. 51.
    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
  52. 52.
    Mittelman A, Chen ZJ, Yang H, Wong GY, Ferrone S. Human high molecular weight melanomaassociated antigen (HMW-MAA) mimicry by mouse anti-idiotypic monoclonal antibody MK2–23: induction of humoral anti-HMW-MAA immunity and prolongation of survival in patients with stage IV melanoma. Proc Nat! Acad Sci USA 1992; 89:466–470.CrossRefGoogle Scholar
  53. 53.
    Timmerman JM, Czerwinski DK, Davis TA, et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 2002; 99:1517–1526.PubMedCrossRefGoogle Scholar
  54. 54.
    Wagner U, Köhler S, Reinartz S, et al. Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. Clin Cancer Res 2001; 7:1154–1162.PubMedGoogle Scholar
  55. 55.
    DiFronzo LA, Gupta RK, Essner R, et al. Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J Clin Oncol 2002; 20:3242–3248.PubMedGoogle Scholar
  56. 56.
    Steplewski Z, Sun LK, Shearman CW, Ghrayeb J, Daddona P, Koprowski H. Biological activity of human-mouse IgG1, IgG2, IgG3, and IgG4 chimeric monoclonal antibodies with antitumor specificity. Proc Natl Acad Sci USA 1988; 85:4852–4856.PubMedCrossRefGoogle Scholar
  57. 57.
    Wettendorff M, Iliopoulos D, Schmoll E, Koprowski H, Herlyn D. Specific detection of antibodies in cancer patients following immunotherapy with anti-idiotype. J Immunol Meth 1989; 116:105–115.CrossRefGoogle Scholar
  58. 58.
    Pfreundschuh MG, Ueda R, Rauterberg EW, Dorken BH, Shiku H. Comparison of multiple rosetting assays for detecting antibody reactivity of different immunoglobulin classes against surface antigens of benign and malignant tissue culture cells. J Immunol Meth 1980; 37:71–81.CrossRefGoogle Scholar
  59. 59.
    Herlyn D, Wettendorff M, Schmoll E, et al. Anti-idiotype immunization of cancer patients: modulation of the immune response. Proc Natl Acad Sci USA 1987; 84:8055–8059.PubMedCrossRefGoogle Scholar
  60. 60.
    Somasundaram R, Zaloudik J, Jacob L, et al. Induction of antigen-specific T and B cell immunity in colon carcinoma patients by anti-idiotypic antibody. J Immunol 1995; 155:3253–3261.PubMedGoogle Scholar
  61. 61.
    Birebent B, Koido T, Mitchell E, et al. Anti-idiotypic antibody (Ab2) vaccines: coupling of Ab2 BR3E4 to KLH increases humoral and/or cellular immune responses in animals and colorectal cancer patients. J Cancer Res Clin Oncol 2001; 127:R27-R33.PubMedCrossRefGoogle Scholar
  62. 62.
    Foon KA, Chakraborty M, John WJ, Sherratt A, Kohler H, Bhattacharya-Chatterjee M. Immune response to the carcinoembryonic antigen in patients treated with an anti-idiotype antibody vaccine. J Clin Invest 1995; 96:334–342.PubMedCrossRefGoogle Scholar
  63. 63.
    Foon KA, John WJ, Chakraborty M, Sherratt A, Garrison J, Flett M, Bhattacharya-Chatterjee M. Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. Clin Cancer Res 1997; 3:1267–1276.PubMedGoogle Scholar
  64. 64.
    Staib L, Birebent B, Somasundaram R, Purev E, Braumüller H, Leeser C, Küttner N, Li W, Zhu D, Diao J, Wunner W, Speicher D, Beger H-G, Song H, Herlyn D. Immunogenicity of recombinant GA733–2E antigen (C017–1A, EGP, KS1–4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients. Int J Cancer 2001; 92:79–87.PubMedCrossRefGoogle Scholar
  65. 65.
    Livingston PO, Albino AP, Chung TJ, Real FX, Houghton AN, Oettgen HF, Old U. Serological response of melanoma patients to vaccines prepared from VSV lysates of autologous and allogeneic cultured melanoma cells. Cancer 1985; 55:713–720.PubMedCrossRefGoogle Scholar
  66. 66.
    Livingston PO, Kaelin K, Pinsky CM, Oettgen HF, Old L. The serologic response of patients with stage II melanoma to allogeneic melanoma cell vaccines. Cancer 1985; 56:2194–2200.PubMedCrossRefGoogle Scholar
  67. 67.
    Morton DL, Hoon DS, Nizze JA, Foshag LJ, Famatiga E, Wanek LA, Chang C, Trie RF, Gupta RK, Elashoff R. Polyvalent melanoma vaccine improves survival of patients with metastatic melanoma. Ann NY Acad Sci 1993; 690:120–134.PubMedCrossRefGoogle Scholar
  68. 68.
    Soiffer R, Lynch T, Mihm M, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 1998; 95:13141–13146.PubMedCrossRefGoogle Scholar
  69. 69.
    Mittelman A, Chen ZJ, Kageshita T, Yang H, Yamada M, Baskind P, Goldberg N, Puccio C, Ahmed T, Arlin Z, Ferrone S. Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weightmelanoma-associated antigen monoclonal antibodies. J Clin Invest 1990; 86:2136–2144.PubMedCrossRefGoogle Scholar
  70. 70.
    Ritter G, Boosfeld E, Adluri R, Calves M, Oettgen HF, Old LJ, Livingston P. 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
  71. 71.
    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
  72. 72.
    Livingston PO, Wong GY, Adluri S, Tao Y, Padavan M, Parente R, Hanlon C, Calves MJ, Helling F, Ritter G, Oettgen HF, Old L. Improved survival in 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
  73. 73.
    Livingston P, Zhang S, Adluri S, Yao TJ, Graeber L, Ragupathi G, Helling F, Fleisher M. Tumor cell reactivity mediated by IgM antibodies in sera from melanoma patients vaccinated with GM2 ganglioside covalently linked to KLH is increased by IgG antibodies. Cancer Immunol Immunother 1997; 43: 324–330.PubMedCrossRefGoogle Scholar
  74. 74.
    Chapman PB, Morrissey DM, Panageas KS, Hamilton WB, Zhan C, Destro AN, Williams L, Israel RJ Livingston PO. Induction of antibodies against GM2 ganglioside by immunizing melanoma patients using GM2-keyhole limpet hemocyanin + QS21 vaccine: a dose-response study. Clin Cancer Res 2000; 6:874–879.PubMedGoogle Scholar
  75. 75.
    Ioannides CG, Platsoucas CD, Bowen JM, Wharton JT, Freedman RS. Increased ovarian tumor cell surface reacting antibodies in patients with ovarian adenocarcinoma after viral oncolysate treatment. Anticancer Res 1989; 9:81–86.PubMedGoogle Scholar
  76. 76.
    Ioannides CG, Platsoucas CD, Patenia R, Kim YP, Bowen JM, Morris M, Edwards C, Wharton JT, Freedman RS. T-cell function in ovarian cancer patients treated with viral oncolysates: I. Increased helper activity to immunoglobulins production. Anticancer Res 1990; 10:645–654.PubMedGoogle Scholar
  77. 77.
    Sabbatini PJ, Kudryashov V, Ragupathi G, et al. Immunization of ovarian cancer patients with a synthetic Lewis-protein conjugate vaccine: a phase I trial. Int J Cancer 2000; 87:79–85.PubMedCrossRefGoogle Scholar
  78. 78.
    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
  79. 79.
    Miller GA, Pontes JE, Huben RP, Goldrosen MH. Humoral immune response of patients receiving specific active immunotherapy for renal cell carcinoma. Cancer Res 1985; 45:4478–4482.PubMedGoogle Scholar
  80. 80.
    Chapman PB, Morrisey D, Panageas KS, Williams L, Lewis JJ, Israel Ri, Hamilton WB, Livingston PO. Vaccination with a bivalent Gm2 and GD2 ganglioside conjugate vaccine: a trial comparing doses of GD2keyhole limpet hemocyanin. Clin Cancer Res 2000; 6:4658–4662.PubMedGoogle Scholar
  81. 81.
    Foon KA, Lutzky J, Baral RN, et al. Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. J Clin Oncol 2000; 18:376–384.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Rajasekharan Somasundaram
  • Tianqian Zhang
  • Dorothee Herlyn

There are no affiliations available

Personalised recommendations