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Allogeneic Antitumor Vaccine Strategies

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Allogeneic Stem Cell Transplantation

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

The tumor immunosurveillance theory, proposed over 30 yr ago as a cellular immune process to protect against the development of cancer (1), was largely abandoned because most cancers develop in the setting of a normal immune system. However, recently the concept was resurrected when it was demonstrated that lymphocytes and interferon γ collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas (2). In addition, it was demonstrated that the immune system selects for cancers with reduced immunogenicity. Therefore, the immune system may function as a tumor-suppressor, and paradoxically, selects for tumors that are more capable of surviving in an immunocompetent host.

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References

  1. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res 1970; 13: 1–27.

    PubMed  CAS  Google Scholar 

  2. Shankaran V, Ikeda H, Bruce AT, White 7M, Swanson PE, Old L7, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001; 410 (6832): 1107–1111.

    Article  PubMed  CAS  Google Scholar 

  3. Old U. Tumor immunology: the first century. Curr Opin Immunol 1992; 4 (5): 603–607.

    Article  PubMed  CAS  Google Scholar 

  4. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas: With a report of ten original cases. Am J Med Sci 1893; 105 (5): 487–511.

    Article  Google Scholar 

  5. Nadler SH, Moore GE. Clinical immunologic study of malignant disease: response to tumor transplants and transfer of leukocytes. Ann Surg 1966; 164 (3): 482–490.

    Article  PubMed  CAS  Google Scholar 

  6. Akporiaye E, Hersh EM. Cancer Vaccines: Clinical Applications. In: Devita VT, Hellman S., Rosenberg SA, eds. Biologic Therapy of Cancer. Lippincott, Philadelphia, PA, 1999, pp. 635–647.

    Google Scholar 

  7. Pardoll DM. Therapeutic vaccination for cancer. Clin Immunol 2000; 95 (1 Pt 2): 544–562.

    Google Scholar 

  8. Barrett J. Allogeneic Immunotherapy for Malignant Diseases. Marcel Dekker, New York, 2000.

    Book  Google Scholar 

  9. Ochsenbein AF, Klenerman P, Karrer U, Ludewig B, Pericin M, Hengartner H, et al. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Nall Acad Sci USA 1999; 96 (5): 2233–2238.

    Article  CAS  Google Scholar 

  10. Mackall CL, Fleisher TA, Brown MR, Magrath IT, Shad AT, Horowitz ME, et al. Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood 1994 84 (7): 2221–2228.

    PubMed  CAS  Google Scholar 

  11. Lum LG. The kinetics of immune reconstitution afterhuman marrow transplantation. Blood 1987; 69 (2): 369–380.

    PubMed  CAS  Google Scholar 

  12. Small TN, Keever CA, Weiner-Fedus S, Heller G, O’ Reilly RJ, Flomenberg N. B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny. Blood 1990; 76 (8): 1647–1656.

    PubMed  CAS  Google Scholar 

  13. Claret EJ, Alyea EP, Orsini E, Pickett CC, Collins H, Wang Y, et al. Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion. J Clin Invest 1997; 100 (4): 855–866.

    Article  PubMed  CAS  Google Scholar 

  14. Dye ES, North RJ. T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases. J Exp Med 1981; 154 (4): 1033–1042.

    Article  PubMed  CAS  Google Scholar 

  15. Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 1999; 163 (10): 5211–5218.

    PubMed  CAS  Google Scholar 

  16. Shevach EM. Regulatory T Cells in Autoimmmunity. Annu Rev Immunol 2000; 18: 423–449.

    Article  PubMed  CAS  Google Scholar 

  17. Ng WF, Duggan PJ, Ponchel F, Matarese G, Lombardi G, Edwards AD, et al. Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells. Blood 2001; 98 (9): 2736–2744.

    Article  PubMed  CAS  Google Scholar 

  18. Woo EY, Chu CS, Goletz TJ, Schlienger K, Coukos G, Rubin SC, et al. Regulatory CD4+CD25+ T cells in tumors from patients with early-stage non small cell lung cancer and late-stage ovarian cancer. Cancer Res 2001; 61: 4766–4772.

    PubMed  CAS  Google Scholar 

  19. Woo EY, Yeh H, Chu CS, Schlienger K, Riley JL, Kaiser LR, et al. Cutting edge: regulatory t cells from cancer patients directly inhibit autologous t cell proliferation. J Immunol 2002; 9: 4272–4276.

    Google Scholar 

  20. Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 2001; 194 (6): 823–832.

    Article  PubMed  CAS  Google Scholar 

  21. Sadovnikova E, Stauss HJ. Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: reagents for tumor immunotherapy. Proc Natl Acad Sci USA 1996;93(23): 13,114–13,118.

    Google Scholar 

  22. Sadovnikova E, Jopling LA, Soo KS, Stauss HJ. Generation of human tumor-reactive cytotoxic T cells against peptides presented by non-self HLA class I molecules. Eur J Immunol 1998; 28 (1): 193–200.

    Article  PubMed  CAS  Google Scholar 

  23. Nisbet NW, Simonsen M, Zaleski M. The frequency of antigen-sensitive cells in tissue transplantation. A commentary on clonal selection. J Exp Med 1969; 129 (3): 459–467.

    Article  PubMed  CAS  Google Scholar 

  24. Suchin EJ, Langmuir PB, Palmer E, Sayegh MH, Wells AD, Turka LA. Quantifying the frequency of alloreactive T cells in vivo: new answers to an old question. J Immunol 2001; 166 (2): 973–981.

    PubMed  CAS  Google Scholar 

  25. Shoskes DA, Wood KJ. Indirect pesentation of MHC antigens in transplantation. Immunol Today 1994; 15: 32–38.

    Article  PubMed  CAS  Google Scholar 

  26. Heath WR, Kurts C, Miller JFAP, Carbone F. Cross-tolerance: a pathway for inducing tolerance to peripheral tissue antigens. J Exp Med 1998; 187: 1549–1553.

    Article  PubMed  CAS  Google Scholar 

  27. Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, et al. Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 2001; 411 (6841): 1058–1064.

    Article  PubMed  CAS  Google Scholar 

  28. Speiser DE, Miranda R, Zakarian A, Bachmann MF, McKall-Faienza K, Odermatt B, et al. Self antigens expressed by solid tumors do not efficiently stimulate naive or activated t cells: implications for immunotherapy. J Exp Med 1997; 186 (5): 645–653.

    Article  PubMed  CAS  Google Scholar 

  29. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994; 264 (5161): 961–965.

    Article  PubMed  CAS  Google Scholar 

  30. Shlomchik WD, Couzens MS, Tang CB, McNiff J, Robert ME, Liu J, et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 1999; 285 (5426): 412–415.

    Article  PubMed  CAS  Google Scholar 

  31. Greten TF, Jaffee EM. Cancer vaccines. J Clin Oncol 1999; 17 (3): 1047–1060.

    PubMed  CAS  Google Scholar 

  32. Hornung RL, Longo DL, Bowersox OC, Kwak LW. Tumor antigen-specific immunization of bone marrow transplantation donors as adoptive therapy against established tumor. JNatl Cancerinst 1995; 87 (17): 1289–1296.

    Article  CAS  Google Scholar 

  33. Pardoll DM. Cancer vaccines. Nat Med 1998; 4 (Suppl 5): 525–531.

    Article  PubMed  CAS  Google Scholar 

  34. Mach N, Dranoff G. Cytokine-secreting tumor cell vaccines. Curr Opin Immunol 2000; 12 (5): 571–575.

    Article  PubMed  CAS  Google Scholar 

  35. Dhodapkar MV, Steinman RM, Sapp M, Desai H, Fossella C, Krasovsky J, et al. Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J Clin Invest 1999; 104 (2): 173–180.

    Article  PubMed  CAS  Google Scholar 

  36. PittetMJ, Speiser DE, Lienard D, Valmori D, Guillaume P, Dutoit V, et al. Expansion and functional maturation of human tumor antigen-specific CD8+ T cells after vaccination with antigenic peptide. Clin Cancer Res 2001; 7 (Suppl 3): 796s - 803s.

    Google Scholar 

  37. Schmidt W, SchweighofferT, Herbst E, Maass G, Berger M, SchilcherF, et al. Cancer vaccines: the interleukin 2 dosage effect. Proc Natl Acad Sci USA 1995; 92 (10): 4711–4714.

    Article  PubMed  CAS  Google Scholar 

  38. Chakraborty NG, Li L, Sporn JR, Kurtzman SH, Ergin MT, Mukherji B. Emergence of regulatory CD4+ T cell response to repetitive stimulation with antigen-presenting cells in vitro: implications in designing antigen-presenting cell-based tumor vaccines. J Immunol 1999; 162 (9): 5576–5583.

    PubMed  CAS  Google Scholar 

  39. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001;193(2):233 238.

    Google Scholar 

  40. Serody JS, Collins EJ, Tisch RM, Kuhns JJ, Frelinger JA. T cell activity after dendritic cell vaccination is dependent on both the type of antigen and the mode of delivery. J Immunol 2000; 164 (9): 4961–4967.

    PubMed  CAS  Google Scholar 

  41. Korver K, Boeschoten EW, Krediet RT, van SG, Schellekens PT. Dose-response effects in immunizations with keyhole limpet haemocyanin and rabies vaccine: shift in some immunodeficiency states. Clin Exp Immunol 1987; 70 (2): 328–335.

    PubMed  CAS  Google Scholar 

  42. Mastrangelo MJ, Lattime EC, Maguire Jr. H, Berd D. Whole Cell Vaccines. In: Devita VT, Hellman S., Rosenberg SA, editors. Biologic Therapy of Cancer. Lippincott, Philadelphia, PA, 1999, pp. 648–659.

    Google Scholar 

  43. Kayaga J, Souberbielle BE, Sheikh N, Morrow WJ, Scott-Taylor T, Vile R, et al. Anti-tumour activity against B 16- F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine. Gene Ther 1999; 6 (8): 1475–1481.

    Article  PubMed  CAS  Google Scholar 

  44. Toes RE, Blom RJ, van d, V, Offringa R, Melief CJ, Kast WM. Protective antitumor immunity induced by immunization with completely allogeneic tumor cells. Cancer Res 1996; 56 (16): 3782–3787.

    PubMed  CAS  Google Scholar 

  45. Clerici M, Stocks NI, Zajac RA, Boswell RN, Via CS, Shearer GM. Circumvention of defective CD4 T helper cell function in HIV-infected individuals by stimulation with HLA alloantigens. J Immunol 1990; 144 (9): 3266–3271.

    PubMed  CAS  Google Scholar 

  46. Fabre JW. The allogeneic response and tumor immunity. Nat Med 2001; 7 (6): 649–652.

    Article  PubMed  CAS  Google Scholar 

  47. Feuerer M, Beckhove P, BaiL, Solomayer EF, Bastert G, Diel IJ, et al. Therapy of human tumors in NOD/S CID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med 2001; 7 (4): 452–458.

    Article  PubMed  CAS  Google Scholar 

  48. Klein C, Bueler H, Mulligan RC. Comparative analysis of genetically modified dendritic cells and tumor cells as therapeutic cancer vaccines. J Exp Med 2000; 191 (10): 1699–1708.

    Article  PubMed  CAS  Google Scholar 

  49. Yang S, Darrow TL, Seigler HF. Generation of primary tumor-specific cytotoxic T lymphocytes from autologous and human lymphocyte antigen class I-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells. Cancer Res 1997; 57 (8): 1561–1568.

    PubMed  CAS  Google Scholar 

  50. Wimperis JZ, Gottlieb D, Duncombe AS, Heslop HE, Prentice HG, Brenner MK. Requirements for the adoptive transfer of antibody responses to a priming antigen in man. J Immunol 1990; 144 (2): 541–547.

    PubMed  CAS  Google Scholar 

  51. Anderson LD, Jr., Petropoulos D, Everse LA, Mullen CA. Enhancement of graft-versus-tumor activity and graft-versus-host disease by pretransplant immunization of allogeneic bone marrow donors with a recipient-derived tumor cell vaccine. Cancer Res 1999; 59 (7): 1525–1530.

    PubMed  CAS  Google Scholar 

  52. Anderson LD, Jr., Savary CA, Mullen CA. Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease. Blood 2000; 95 (7): 2426–2433.

    PubMed  CAS  Google Scholar 

  53. Anderson LD, Jr., Mori S, Mann S, Savary CA, Mullen CA. Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease. Cancer Res 2000; 60 (20): 5797–5802.

    PubMed  CAS  Google Scholar 

  54. Teshima T, Mach N, Hill GR, Pan L, Gillessen S, Dranoff G, et al. Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation. Cancer Res 2001; 61 (1): 162–171.

    PubMed  CAS  Google Scholar 

  55. Mastrangelo MJ, Berd D, Maguire H, Jr. The immunoaugmenting effects of cancer chemotherapeutic agents. Semin Oncol 1986; 13 (2): 186–194.

    PubMed  CAS  Google Scholar 

  56. Machiels JP, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, et al. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res 2001; 61 (9): 3689–3697.

    PubMed  CAS  Google Scholar 

  57. Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol 1996; 156 (12): 4609–4616.

    PubMed  CAS  Google Scholar 

  58. Borrello I, Sotomayor EM, Rattis FM, Cooke SK, Gu L, Levitsky HI. Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)producing tumor vaccines. Blood 2000; 95 (10): 3011–3019.

    PubMed  CAS  Google Scholar 

  59. Soloski MJ. Recognition of tumor cells by the innate immune system. Curr Opin Immunol 2001; 13 (2): 154–162.

    Article  PubMed  CAS  Google Scholar 

  60. Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rael and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001; 413 (6852): 165–171.

    Article  PubMed  CAS  Google Scholar 

  61. Murphy WJ, Longo DL. The potential role of NK cells in the separation of graft-versus-tumor effects from graft-versus-host disease after allogeneic bone marrow transplantation. Immunol Rev 1997; 157: 167–176.

    Article  PubMed  CAS  Google Scholar 

  62. Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA, Pennington R, et al. Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med 1999; 5 (10): 1171–1177.

    Article  PubMed  CAS  Google Scholar 

  63. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med 1996; 2 (1): 52–58.

    Article  PubMed  CAS  Google Scholar 

  64. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells. Nat Med 1998;4(3):328 332.

    Google Scholar 

  65. Childs RW, Clave E, Tisdale J, Plante M, Hensel N, Barrett J. Successful treatment of metastatic renal cell carcinoma with a nonmyeloablative allogeneic peripheral-blood progenitor-cell transplant: evidence for a graft-versus-tumor effect. J Clin Oncol 1999; 17 (7): 2044.

    Google Scholar 

  66. Luznik L, Slansky JE, Bonello I, Levitsky HI, Pardoll DM, Fuchs EJ. Successful therapy of metastatic cancer with GM -CSF based tumor cell vaccines after non-myeloablative allogeneic stem cell transplantation. Submitted for publication.

    Google Scholar 

  67. Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Bros sart P, et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med 2000; 6 (3): 332–336.

    Article  PubMed  CAS  Google Scholar 

  68. Horowitz MM, Rowlings PA. An update from the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry on current activity in hematopoietic stem cell transplantation. Curr Opin Hematol 1997; 4 (6): 395–400.

    Article  PubMed  CAS  Google Scholar 

  69. Asai O, Longo DL, Tian ZG, Hornung RL, Taub DD, Ruscetti FW, et al. Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation. J Clin Invest 1998; 101 (9): 1835–1842.

    Article  PubMed  CAS  Google Scholar 

  70. Krenger W, Snyder KM, Byon JC, Falzarano G, Ferrara JL. Polarized type 2 alloreactive CD4+ and CD8+ donor T cells fail to induce experimental acute graft-versus-host disease. Jlmmunol 1995; 155 (2): 585–593.

    CAS  Google Scholar 

  71. Fowler DH, Breglio J, Nagel G, Eckhaus MA, Gress RE. Allospecific CD8+ Tcl and Tc2 populations in graftversus-leukemia effect and graft-versus-host disease. J Immunol 1996; 157 (11): 4811–4821.

    PubMed  CAS  Google Scholar 

  72. Fowler DH, Gress RE. Th2 and Tc2 cells in the regulation of GVHD, GVL, and graft rejection: considerations for the allogeneic transplantation therapy of leukemia and lymphoma. Leuk Lymph 2000; 38 (3–4): 221–234.

    Article  CAS  Google Scholar 

  73. Rosenberg SA, White DE. Vitiligo in patients with melanoma: normal tissue antigens can be targets for cancer immunotherapy. J Immunother Emphasis Tumor Immunol 1996; 19 (1): 81–84.

    Article  PubMed  CAS  Google Scholar 

  74. Okamoto T, Irie RF, Fujii S, Huang SK, Nizze AJ, Morton DL, et al. Anti-tyrosinase-related protein-2 immune response in vitiligo patients and melanoma patients receiving active-specific immunotherapy. JlnvestDermatol 1998; 111 (6): 1034–1039.

    CAS  Google Scholar 

  75. Donaldson RC, Canaan SA, Jr., McLean RB, Ackerman LV. Uveitis and vitiligo associated with BCG treatment for malignant melanoma. Surgery 1974; 76 (5): 771–778.

    PubMed  CAS  Google Scholar 

  76. Allison AC, Byars NE. Immunological adjuvants: desirable properties and side-effects. Mol Immunol 1991; 28 (3): 279–284.

    Article  PubMed  CAS  Google Scholar 

  77. Albert ML, Darnell JC, Bender A, Francisco LM, Bhardwaj N, Darnell RB. Tumor-specific killer cells in paraneoplastic cerebellar degeneration. Nat Med 1998; 4 (11): 1321–1324.

    Article  PubMed  CAS  Google Scholar 

  78. Livingston PO, Ragupathi G, Musselli C. Autoimmune and antitumor consequences of antibodies against antigens shared by normal and malignant tissues. J Clin Immunol 2000; 20 (2): 85–93.

    Article  PubMed  CAS  Google Scholar 

  79. Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol 2001; 19: 275–290.

    Article  PubMed  CAS  Google Scholar 

  80. Simon RM, Steinberg SM, Hamilton M, Hildesheim A, Khleif S, Kwak LW, et al. Clinical trial designs for the early clinical development of therapeutic cancer vaccines. J Clin Oncol 2001; 19 (6): 1848–1854.

    PubMed  CAS  Google Scholar 

  81. Mackall CL, Gress RE. Pathways of T-cell regeneration in mice and humans: implications for bone marrow transplantation and immunotherapy. Immunol Rev 1997; 157: 61–72.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Ginna G. Laport
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  2. Carl H. June
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Editors and Affiliations

  1. Allogeneic Transplant Program, Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA

    Mary J. Laughlin MD

  2. Blood and Marrow Transplant Program, Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH, USA

    Hillard M. Lazarus MD

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Laport, G.G., June, C.H. (2003). Allogeneic Antitumor Vaccine Strategies. In: Laughlin, M.J., Lazarus, H.M. (eds) Allogeneic Stem Cell Transplantation. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-333-0_18

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  • DOI: https://doi.org/10.1007/978-1-59259-333-0_18

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