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Cytokine-Based Therapy for Cancer

  • Chapter
Molecular Targeting in Oncology

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Summary

Cytokine therapy has been extensively investigated in the treatment of malignancies. However, only a few agents, such as interferon and interleukin-2, have proven to have sufficient clinical benefit to justify their more widespread use. This chapter reviews the biology and clinical data for cytokine-based therapies that have been approved for clinical use, as well as cytokines that are currently under investigation.

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References

  1. Kaplan, D.H., et al., Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA, 1998. 95(13): p. 7556–61.

    Article  PubMed  CAS  Google Scholar 

  2. Picaud, S., et al., Enhanced tumor development in mice lacking a functional type I interferon receptor. J Interferon Cytokine Res, 2002. 22(4): p. 457–62.

    Article  PubMed  CAS  Google Scholar 

  3. Shankaran, V., et al., IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature, 2001. 410(6832): p. 1107–11.

    Article  PubMed  CAS  Google Scholar 

  4. Street, S.E., E. Cretney, and M.J. Smyth, Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood, 2001. 97(1): p. 192–7.

    Article  PubMed  CAS  Google Scholar 

  5. Street, S.E., et al., Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med, 2002. 196(1): p. 129–34.

    Article  PubMed  CAS  Google Scholar 

  6. Abbas, A.K., A.H. Lichtman, and J.S. Pober. Cellular and Molecular Immunology. W.B. Saunders company; Philadelphia, PA 19103 4th edition (May 15, 2000).

    Google Scholar 

  7. Pestka, S., C.D. Krause, and M.R. Walter, Interferons, interferon-like cytokines, and their receptors. Immunol Rev, 2004. 202: p. 8–32.

    Article  PubMed  CAS  Google Scholar 

  8. Pestka, S., et al., Interferons and their actions. Annu Rev Biochem, 1987. 56: p. 727–77.

    Article  PubMed  CAS  Google Scholar 

  9. Stewart, W.E., 2nd, Interferon nomenclature recommendations. J Infect Dis, 1980. 142(4): p. 643.

    Google Scholar 

  10. Isaacs, A. and J. Lindenmann, Virus interference. I. The interferon. J Interferon Res, 1987. 7(5): p. 429–38.

    PubMed  CAS  Google Scholar 

  11. Muller, U., et al., Functional role of type I and type II interferons in antiviral defense. Science, 1994. 264(5167): p. 1918–21.

    Article  PubMed  CAS  Google Scholar 

  12. Basham, T.Y., et al., Interferon increases HLA synthesis in melanoma cells: interferon-resistant and -sensitive cell lines. Proc Natl Acad Sci USA, 1982. 79(10): p. 3265–9.

    Article  PubMed  CAS  Google Scholar 

  13. Dolei, A., M.R. Capobianchi, and F. Ameglio, Human interferon-gamma enhances the expression of class I and class II major histocompatibility complex products in neoplastic cells more effectively than interferon-alpha and interferon-beta. Infect Immun, 1983. 40(1): p. 172–6.

    PubMed  CAS  Google Scholar 

  14. Herberman, R.B., et al., Effect of human recombinant interferon on cytotoxic activity of natural killer (NK) cells and monocytes. Cell Immunol, 1982. 67(1): p. 160–7.

    Article  PubMed  CAS  Google Scholar 

  15. Ortaldo, J.R., et al., Effects of several species of human leukocyte interferon on cytotoxic activity of NK cells and monocytes. Int J Cancer, 1983. 31(3): p. 285–9.

    Article  PubMed  CAS  Google Scholar 

  16. Ortaldo, J.R., et al., Effects of recombinant and hybrid recombinant human leukocyte interferons on cytotoxic activity of natural killer cells. J Biol Chem, 1983. 258(24): p. 15011–5.

    PubMed  CAS  Google Scholar 

  17. Wagner, T.C., et al., Interferon receptor expression regulates the antiproliferative effects of interferons on cancer cells and solid tumors. Int J Cancer, 2004. 111(1): p. 32–42.

    Article  PubMed  CAS  Google Scholar 

  18. Clemens, M.J., Interferons and apoptosis. J Interferon Cytokine Res, 2003. 23(6): p. 277–92.

    Article  PubMed  CAS  Google Scholar 

  19. Sidky, Y.A. and E.C. Borden, Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced vascular responses. Cancer Res, 1987. 47(19): p. 5155–61.

    PubMed  CAS  Google Scholar 

  20. Tsuruoka, N., et al., Inhibition of in vitro angiogenesis by lymphotoxin and interferon-gamma. Biochem Biophys Res Commun, 1988. 155(1): p. 429–35.

    Article  PubMed  CAS  Google Scholar 

  21. Dunn, G.P., et al., A critical function for type I interferons in cancer immunoediting. Nat Immunol, 2005. 6(7): p. 722–9.

    Article  PubMed  CAS  Google Scholar 

  22. Greenberg, H.B., et al., Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med, 1976. 295(10): p. 517–22.

    Article  PubMed  CAS  Google Scholar 

  23. Krown, S.E., et al., Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi’s sarcoma. N Engl J Med, 1983. 308(18): p. 1071–6.

    Article  PubMed  CAS  Google Scholar 

  24. Talpaz, M., et al., Chronic myelogenous leukaemia: haematological remissions with alpha interferon. Br J Haematol, 1986. 64(1): p. 87–95.

    PubMed  CAS  Google Scholar 

  25. Harris, J.M., N.E. Martin, and M. Modi, Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet, 2001. 40(7): p. 539–51.

    Article  PubMed  CAS  Google Scholar 

  26. Reddy, K.R., Development and pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a (40 kD). Semin Liver Dis, 2004. 24(Suppl 2): p. 33–8.

    Article  Google Scholar 

  27. Youngster, S., et al., Structure, biology, and therapeutic implications of pegylated interferon alpha-2b. Curr Pharm Des, 2002. 8(24): p. 2139–57.

    Article  PubMed  CAS  Google Scholar 

  28. Motzer, R.J., et al., Phase II trial of branched peginterferon-alpha 2a (40 kDa) for patients with advanced renal cell carcinoma. Ann Oncol, 2002. 13(11): p. 1799–805.

    Article  PubMed  CAS  Google Scholar 

  29. Talpaz, M., et al., Phase 1 study of polyethylene glycol formulation of interferon alpha-2B (Schering 54031) in Philadelphia chromosome-positive chronic myelogenous leukemia. Blood, 2001. 98(6): p. 1708–13.

    Article  PubMed  CAS  Google Scholar 

  30. Nagai, M. and T. Arai, Clinical effect of interferon in malignant brain tumours. Neurosurg Rev, 1984. 7(1): p. 55–64.

    Article  PubMed  CAS  Google Scholar 

  31. Bukowski, R.M., et al., Phase I trial of natural human interferon beta in metastatic malignancy. Cancer Res, 1991. 51(3): p. 836–40.

    PubMed  CAS  Google Scholar 

  32. Aulitzky, W.E., et al., Divergent in vivo and in vitro antileukemic activity of recombinant interferon beta in patients with chronic-phase chronic myelogenous leukemia. Ann Hematol, 1993. 67(5): p. 205–11.

    Article  PubMed  CAS  Google Scholar 

  33. Carnaud, C., et al., Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol, 1999. 163(9): p. 4647–50.

    PubMed  CAS  Google Scholar 

  34. Frucht, D.M., et al., IFN-gamma production by antigen-presenting cells: mechanisms emerge. Trends Immunol, 2001. 22(10): p. 556–60.

    Article  PubMed  CAS  Google Scholar 

  35. Harris, D.P., et al., Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol, 2000. 1(6): p. 475–82.

    Article  PubMed  CAS  Google Scholar 

  36. Yoshimoto, T., et al., IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol, 1998. 161(7): p. 3400–7.

    PubMed  CAS  Google Scholar 

  37. Boehm, U., et al., Cellular responses to interferon-gamma. Annu Rev Immunol, 1997. 15: p. 749–95.

    Article  PubMed  CAS  Google Scholar 

  38. Freedman, A.S., et al., Selective induction of B7/BB-1 on interferon-gamma stimulated monocytes: a potential mechanism for amplification of T cell activation through the CD28 pathway. Cell Immunol, 1991. 137(2): p. 429–37.

    Article  PubMed  CAS  Google Scholar 

  39. Wallach, D., M. Fellous, and M. Revel, Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature, 1982. 299(5886): p. 833–6.

    Article  PubMed  CAS  Google Scholar 

  40. Groettrup, M., et al., Interferon-gamma inducible exchanges of 20S proteasome active site subunits: why? Biochimie, 2001. 83(3–4): p. 367–72.

    Google Scholar 

  41. Groettrup, M., et al., A third interferon-gamma-induced subunit exchange in the 20S proteasome. Eur J Immunol, 1996. 26(4): p. 863–9.

    Article  PubMed  CAS  Google Scholar 

  42. Hisamatsu, H., et al., Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma. J Exp Med, 1996. 183(4): p. 1807–16.

    Article  PubMed  CAS  Google Scholar 

  43. Gajewski, T.F. and F.W. Fitch, Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol, 1988. 140(12): p. 4245–52.

    PubMed  CAS  Google Scholar 

  44. Snapper, C.M. and W.E. Paul, Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science, 1987. 236(4804): p. 944–7.

    Article  PubMed  CAS  Google Scholar 

  45. Dighe, A.S., et al., Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity, 1994. 1(6): p. 447–56.

    Article  PubMed  CAS  Google Scholar 

  46. Coughlin, C.M., et al., Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity, 1998. 9(1): p. 25–34.

    Article  PubMed  CAS  Google Scholar 

  47. Friesel, R., A. Komoriya, and T. Maciag, Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol, 1987. {104}(3): p. 689–96.

    Article  PubMed  CAS  Google Scholar 

  48. Pfizenmaier, K., et al., Differential gamma-interferon response of human colon carcinoma cells: inhibition of proliferation and modulation of immunogenicity as independent effects of gamma-interferon on tumor cell growth. Cancer Res, 1985. {45}(8): p. 3503–9.

    PubMed  CAS  Google Scholar 

  49. Ratliff, T.L., et al., Inhibition of mouse bladder tumor proliferation by murine interferon-gamma and its synergism with interferon-beta. Cancer Res, 1984. {44}(10): p. 4377–81.

    PubMed  CAS  Google Scholar 

  50. Rubin, B.Y., V. Sekar, and W.A. Martimucci, Comparative antiproliferative efficacies of human alpha and gamma interferons. J Gen Virol, 1983. {64}(8): p. 1743–8.

    Google Scholar 

  51. Elhilali, M.M., et al., Placebo-associated remissions in a multicentre, randomized, double-blind trial of interferon gamma-1b for the treatment of metastatic renal cell carcinoma. The Canadian Urologic Oncology Group. BJU Int, 2000. {86}(6): p. 613–8.

    CAS  Google Scholar 

  52. Koziner, B., et al., Double-blind prospective randomized comparison of interferon gamma-1b versus placebo after autologous stem cell transplantation. Acta Haematol, 2002. {108}(2): p. 66–73.

    Article  PubMed  CAS  Google Scholar 

  53. Small, E.J., et al., The treatment of metastatic renal cell carcinoma patients with recombinant human gamma interferon. Cancer J Sci Am, 1998. {4}(3): p. 162–7.

    PubMed  CAS  Google Scholar 

  54. Todd, P.A. and K.L. Goa, Interferon gamma-1b. A review of its pharmacology and therapeutic potential in chronic granulomatous disease. Drugs, 1992. {43}(1): p. 111–22.

    PubMed  CAS  Google Scholar 

  55. Golomb, H.M., et al., Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. J Clin Oncol, 1986. {4}(6): p. 900–5.

    PubMed  CAS  Google Scholar 

  56. Quesada, J.R., et al., Treatment of hairy cell leukemia with recombinant alpha-interferon. Blood, 1986. {68}(2): p. 493–7.

    PubMed  CAS  Google Scholar 

  57. Golomb, H.M., et al., Interferon treatment for hairy cell leukemia: an update on a cohort of 69 patients treated from 1983–1986. Leukemia, 1992. {6}(11): p. 1177–80.

    PubMed  CAS  Google Scholar 

  58. Dadmarz, R., et al., The mechanism of action of interferon-alpha (IFN-alpha) in hairy-cell leukaemia; Hu-IFN-alpha 2 receptor expression by hairy cells and other normal and leukaemic cell types. Leuk Res, 1986. {10}(11): p. 1279–85.

    Article  PubMed  CAS  Google Scholar 

  59. Paganelli, K.A., et al., B cell growth factor-induced proliferation of hairy cell lymphocytes and inhibition by type I interferon in vitro. Blood, 1986. {67}(4): p. 937–42.

    PubMed  CAS  Google Scholar 

  60. Huber, C., et al., Studies on the optimal dose and the mode of action of alpha-interferon in the treatment of hairy cell leukemia. Leukemia, 1987. {1}(4): p. 355–7.

    PubMed  CAS  Google Scholar 

  61. Goodman, G.R., et al., Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol, 2003. {21}(5): p. 891–6.

    Article  PubMed  Google Scholar 

  62. Seymour, J.F., et al., Response to interferon-alpha in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine. Leukemia, 1995. {9}(5): p. 929–32.

    PubMed  CAS  Google Scholar 

  63. Talpaz, M., et al., Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia. N Engl J Med, 1986. {314}(17): p. 1065–9.

    Article  PubMed  CAS  Google Scholar 

  64. Talpaz, M., et al., Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood, 1983. {62}(3): p. 689–92.

    PubMed  CAS  Google Scholar 

  65. The Italian Cooperative Study Group on Chronic Myeloid Leukemia, Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med, 1994. {330}(12): p. 820–5.

    Article  Google Scholar 

  66. Allan, N.C., S.M. Richards, and P.C. Shepherd, UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Council’s Working Parties for Therapeutic Trials in Adult Leukaemia. Lancet, 1995. {345}(8962): p. 1392–7.

    Article  PubMed  CAS  Google Scholar 

  67. Broustet, A., et al., Hydroxyurea versus interferon alfa-2b in chronic myelogenous leukaemia: preliminary results of an open French multicentre randomized study. Eur J Cancer, 1991. {27}(Suppl 4): p. S18–21.

    Google Scholar 

  68. Hehlmann, R., et al., Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood, 1994. {84}(12): p. 4064–77.

    PubMed  CAS  Google Scholar 

  69. Ohnishi, K., et al., A randomized trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase. Blood, 1995. {86}(3): p. 906–16.

    PubMed  CAS  Google Scholar 

  70. The Italian Cooperative Study Group on Chronic Myeloid Leukemia, Long-term follow-Up of the italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia. Blood, 1998. {92}(5): p. 1541–8.

    Google Scholar 

  71. Hehlmann, R., et al., Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea. Leukemia, 2003. {17}(8): p. 1529–37.

    Article  PubMed  CAS  Google Scholar 

  72. Chronic Myeloid Leukemia Trialists’ Collaborative Group, Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials. J Natl Cancer Inst, 1997. {89}(21): p. 1616–20.

    Article  Google Scholar 

  73. Yasukawa, M., et al., CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner. Blood, 1998. {92}(9): p. 3355–61.

    PubMed  CAS  Google Scholar 

  74. Aswald, J.M., J.H. Lipton, and H.A. Messner, Intracellular cytokine analysis of interferon-gamma in T cells of patients with chronic myeloid leukemia. Cytokines Cell Mol Ther, 2002. {7}(2): p. 75–82.

    Article  PubMed  CAS  Google Scholar 

  75. Nicolson, N.L., M. Talpaz, and G.L. Nicolson, Interferon-alpha directly inhibits DNA polymerase activity in isolated chromatin nucleoprotein complexes: correlation with IFN-alpha treatment outcome in patients with chronic myelogenous leukemia. Gene, 1995. {159}(1): p. 105–11.

    Article  PubMed  CAS  Google Scholar 

  76. Kuhr, T., et al., A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML). Leuk Res, 2003. {27}(5): p. 405–11.

    Article  PubMed  CAS  Google Scholar 

  77. Giles, F.J., et al., A prospective randomized study of alpha-2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukemia: the International Oncology Study Group CML1 study. Leuk Lymphoma, 2000. {37}(3–4): p. 367–77.

    PubMed  CAS  Google Scholar 

  78. Guilhot, F., et al., Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med, 1997. {337}(4): p. 223–9.

    Article  PubMed  CAS  Google Scholar 

  79. Anstrom, K.J., et al., Long-term survival estimates for imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia. Cancer, 2004. {101}(11): p. 2584–92.

    Article  PubMed  CAS  Google Scholar 

  80. O’Brien, S.G. and M.W. Deininger, Imatinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia. Semin Hematol, 2003. {40}(2): p. 26–30.

    Article  PubMed  CAS  Google Scholar 

  81. Kantarjian, H.M., et al., Imatinib mesylate therapy improves survival in patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in the chronic phase: comparison with historic data. Cancer, 2003. {98}(12): p. 2636–42.

    Article  PubMed  CAS  Google Scholar 

  82. Branford, S., et al., Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia, 2003. {17}(12): p. 2401–9.

    Article  PubMed  CAS  Google Scholar 

  83. Foon, K.A., et al., Treatment of advanced non-Hodgkin’s lymphoma with recombinant leukocyte A interferon. N Engl J Med, 1984. {311}(18): p. 1148–52.

    Article  PubMed  CAS  Google Scholar 

  84. Siegert, W., et al., Treatment of non-hodgkin’s lymphoma of low-grade malignancy with human fibroblast interferon. Anticancer Res, 1982. {2}(4): p. 193–8.

    PubMed  CAS  Google Scholar 

  85. Louie, A.C., et al., Follow-up observations on the effect of human leukocyte interferon in non-Hodgkin’s lymphoma. Blood, 1981. {58}(4): p. 712–8.

    PubMed  CAS  Google Scholar 

  86. Solal-Celigny, P., et al., Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the Groupe d’Etude des Lymphomes Folliculaires 86 Trial. J Clin Oncol, 1998. {16}(7): p. 2332–8.

    PubMed  CAS  Google Scholar 

  87. Solal-Celigny, P., et al., Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d’Etude des Lymphomes de l’Adulte. N Engl J Med, 1993. {329}(22): p. 1608–14.

    Article  PubMed  CAS  Google Scholar 

  88. Rohatiner, A.Z., et al., Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol, 2005. {23}(10): p. 2215–23.

    Article  PubMed  CAS  Google Scholar 

  89. Fisher, R.I., et al., Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin’s lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. J Clin Oncol, 2000. {18}(10): p. 2010–6.

    PubMed  CAS  Google Scholar 

  90. Barnetson, R.S. and G.M. Halliday, Regression in skin tumours: a common phenomenon. Australas J Dermatol, 1997. {38}(Suppl 1): p. S63–5.

    Google Scholar 

  91. Chang, P. and W.H. Knapper, Metastatic melanoma of unknown primary. Cancer, 1982. {49}(6): p. 1106–11.

    Article  PubMed  CAS  Google Scholar 

  92. Panagopoulos, E. and D. Murray, Metastatic malignant melanoma of unknown primary origin: a study of 30 cases. J Surg Oncol, 1983. {23}(1): p. 8–10.

    Article  PubMed  CAS  Google Scholar 

  93. Norman, J., et al., Metastatic melanoma with an unknown primary. Ann Plast Surg, 1992. {28}(1): p. 81–4.

    Article  PubMed  CAS  Google Scholar 

  94. Reintgen, D.S., et al., Metastatic malignant melanoma with an unknown primary. Surg Gynecol Obstet, 1983. {156}(3): p. 335–40.

    PubMed  CAS  Google Scholar 

  95. Gromet, M.A., W.L. Epstein, and M.S. Blois, The regressing thin malignant melanoma: a distinctive lesion with metastatic potential. Cancer, 1978. {42}(5): p. 2282–92.

    Article  PubMed  CAS  Google Scholar 

  96. Baab, G.H. and C.M. McBride, Malignant melanoma: the patient with an unknown site of primary origin. Arch Surg, 1975. {110}(8): p. 896–900.

    PubMed  CAS  Google Scholar 

  97. King, M., D. Spooner, and D.C. Rowlands, Spontaneous regression of metastatic malignant melanoma of the parotid gland and neck lymph nodes: a case report and a review of the literature. Clin Oncol (R Coll Radiol), 2001. {13}(6): p. 466–9.

    CAS  Google Scholar 

  98. Coates, A., et al., Phase-II study of recombinant alpha 2-interferon in advanced malignant melanoma. J Interferon Res, 1986. {6}(1): p. 1–4.

    PubMed  CAS  Google Scholar 

  99. Creagan, E.T., et al., Phase II study of recombinant leukocyte A interferon (rIFN-alpha A) in disseminated malignant melanoma. Cancer, 1984. {54}(12): p. 2844–9.

    Article  PubMed  CAS  Google Scholar 

  100. Dorval, T., et al., Clinical phase II trial of recombinant DNA interferon (interferon alpha 2b) in patients with metastatic malignant melanoma. Cancer, 1986. {58}(2): p. 215–8.

    PubMed  CAS  Google Scholar 

  101. Hersey, P., et al., Effects of recombinant leukocyte interferon (rIFN-alpha A) on tumour growth and immune responses in patients with metastatic melanoma. Br J Cancer, 1985. {51}(6): p. 815–26.

    PubMed  CAS  Google Scholar 

  102. Mughal, T.I., et al., Role of recombinant interferon alpha 2 and cimetidine in patients with advanced malignant melanoma. J Cancer Res Clin Oncol, 1988. {114}(1): p. 108–9.

    Article  PubMed  CAS  Google Scholar 

  103. Neefe, J.R., et al., Phase II study of recombinant alpha-interferon in malignant melanoma. Am J Clin Oncol, 1990. {13}(6): p. 472–6.

    Article  PubMed  CAS  Google Scholar 

  104. Robinson, W.A., et al., Treatment of metastatic malignant melanoma with recombinant interferon alpha 2. Immunobiology, 1986. {172}(3–5): p. 275–82.

    Google Scholar 

  105. Sertoli, M.R., et al., Phase II trial of recombinant alpha-2b interferon in the treatment of metastatic skin melanoma. Oncology, 1989. {46}(2): p. 96–8.

    PubMed  CAS  Google Scholar 

  106. Steiner, A., C. Wolf, and H. Pehamberger, Comparison of the effects of three different treatment regimens of recombinant interferons (r-IFN alpha, r-IFN gamma, and r-IFN alpha + cimetidine) in disseminated malignant melanoma. J Cancer Res Clin Oncol, 1987. {113}(5): p. 459–65.

    Article  PubMed  CAS  Google Scholar 

  107. Decatris, M., S. Santhanam, and K. O’Byrne, Potential of interferon-alpha in solid tumours: part 1. BioDrugs, 2002. {16}(4): p. 261–81.

    Article  PubMed  CAS  Google Scholar 

  108. Legha, S.S., et al., Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules. J Clin Oncol, 1987. {5}(8): p. 1240–6.

    PubMed  CAS  Google Scholar 

  109. Falkson, C.I., et al., Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol, 1998. {16}(5): p. 1743–51.

    PubMed  CAS  Google Scholar 

  110. Creagan, E.T., et al., Recombinant leukocyte A interferon (rIFN-alpha A) in the treatment of disseminated malignant melanoma. Analysis of complete and long-term responding patients. Cancer, 1986. {58}(12): p. 2576–8.

    Article  PubMed  CAS  Google Scholar 

  111. Eggermont, A.M., et al., Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial. Lancet, 2005. {366}(9492): p. 1189–96.

    Article  PubMed  CAS  Google Scholar 

  112. Grob, J.J., et al., Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet, 1998. {351}(9120): p. 1905–10.

    Article  PubMed  CAS  Google Scholar 

  113. Castello, G., et al., Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma. Melanoma Res, 1993. {3}(1): p. 43–9.

    Article  PubMed  CAS  Google Scholar 

  114. Creagan, E.T., et al., Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma. J Clin Oncol, 1995. {13}(11): p. 2776–83.

    PubMed  CAS  Google Scholar 

  115. Kleeberg, U.R., et al., Final results of the EORTC 18871/DKG 80–1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer, 2004. {40}(3): p. 390–402.

    Article  PubMed  CAS  Google Scholar 

  116. Pehamberger, H., et al., Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. J Clin Oncol, 1998. {16}(4): p. 1425–9.

    PubMed  CAS  Google Scholar 

  117. Cameron, D.A., et al., Adjuvant interferon alpha 2b in high risk melanoma - the Scottish study. Br J Cancer, 2001. {84}(9): p. 1146–9.

    Article  PubMed  CAS  Google Scholar 

  118. Hancock, B.W., et al., Adjuvant interferon in high-risk melanoma: the AIM HIGH Study–United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma. J Clin Oncol, 2004. {22}(1): p. 53–61.

    Article  PubMed  CAS  Google Scholar 

  119. Kirkwood, J.M., et al., High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol, 2001. {19}(9): p. 2370–80.

    PubMed  CAS  Google Scholar 

  120. Kirkwood, J.M., et al., High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol, 2000. {18}(12): p. 2444–58.

    PubMed  CAS  Google Scholar 

  121. Hillner, B.E., et al., Economic analysis of adjuvant interferon alfa-2b in high-risk melanoma based on projections from Eastern Cooperative Oncology Group 1684. J Clin Oncol, 1997. {15}(6): p. 2351–8.

    PubMed  CAS  Google Scholar 

  122. Kirkwood, J.M., et al., Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol, 1996. {14}(1): p. 7–17.

    PubMed  CAS  Google Scholar 

  123. Kirkwood, J.M., et al., A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res, 2004. {10}(5): p. 1670–7.

    Article  PubMed  CAS  Google Scholar 

  124. Falkson, C.I., G. Falkson, and H.C. Falkson, Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol, 1991. {9}(8): p. 1403–8.

    PubMed  CAS  Google Scholar 

  125. Thomson, D.B., et al., Interferon-alpha 2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial. Melanoma Res, 1993. {3}(2): p. 133–8.

    PubMed  CAS  Google Scholar 

  126. Bajetta, E., et al., Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma. J Clin Oncol, 1994. {12}(4): p. 806–11.

    PubMed  CAS  Google Scholar 

  127. Creagan, E.T., et al., A phase I-II trial of the combination of recombinant leukocyte A interferon and recombinant human interferon-gamma in patients with metastatic malignant melanoma. Cancer, 1988. {62}(12): p. 2472–4.

    Article  PubMed  CAS  Google Scholar 

  128. deKernion, J.B., et al., The treatment of renal cell carcinoma with human leukocyte alpha-interferon. J Urol, 1983. {130}(6): p. 1063–6.

    PubMed  CAS  Google Scholar 

  129. Quesada, J.R., D.A. Swanson, and J.U. Gutterman, Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. J Clin Oncol, 1985. {3}(8): p. 1086–92.

    PubMed  CAS  Google Scholar 

  130. Quesada, J.R., et al., Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. J Clin Oncol, 1985. {3}(11): p. 1522–8.

    PubMed  CAS  Google Scholar 

  131. Kempf, R.A., et al., Recombinant interferon alpha-2 (INTRON A) in a phase II study of renal cell carcinoma. J Biol Response Mod, 1986. {5}(1): p. 27–35.

    PubMed  CAS  Google Scholar 

  132. Umeda, T. and T. Niijima, Phase II study of alpha interferon on renal cell carcinoma. Summary of three collaborative trials. Cancer, 1986. {58}(6): p. 1231–5.

    Article  PubMed  CAS  Google Scholar 

  133. Trump, D.L., et al., High-dose lymphoblastoid interferon in advanced renal cell carcinoma: an Eastern Cooperative Oncology Group Study. Cancer Treat Rep, 1987. {71}(2): p. 165–9.

    PubMed  CAS  Google Scholar 

  134. Muss, H.B., et al., Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration. J Clin Oncol, 1987. {5}(2): p. 286–91.

    PubMed  CAS  Google Scholar 

  135. Porzsolt, F., et al., Treatment of advanced renal cell cancer with recombinant interferon alpha as a single agent and in combination with medroxyprogesterone acetate. A randomized multicenter trial. J Cancer Res Clin Oncol, 1988. {114}(1): p. 95–100.

    Article  PubMed  CAS  Google Scholar 

  136. Steineck, G., et al., Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial. Acta Oncol, 1990. {29}(2): p. 155–62.

    PubMed  CAS  Google Scholar 

  137. Minasian, L.M., et al., Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol, 1993. {11}(7): p. 1368–75.

    PubMed  CAS  Google Scholar 

  138. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet, 1999. {353}(9146): p. 14–7.

    Article  Google Scholar 

  139. Kirkwood, J.M., et al., A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial. Cancer Res, 1985. {45}(2): p. 863–71.

    PubMed  CAS  Google Scholar 

  140. Flanigan, R.C., et al., Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med, 2001. {345}(23): p. 1655–9.

    Article  PubMed  CAS  Google Scholar 

  141. Pizzocaro, G., et al., Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J Clin Oncol, 2001. {19}(2): p. 425–31.

    PubMed  CAS  Google Scholar 

  142. Kriegmair, M., R. Oberneder, and A. Hofstetter, Interferon alfa and vinblastine versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma. Urology, 1995. {45}(5): p. 758–62.

    Article  PubMed  CAS  Google Scholar 

  143. Fossa, S.D., et al., Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol, 1992. {3}(4): p. 301–5.

    PubMed  CAS  Google Scholar 

  144. Nanus, D.M., et al., Interaction of retinoic acid and interferon in renal cancer cell lines. J Interferon Cytokine Res, 2000. {20}(9): p. 787–94.

    Article  PubMed  CAS  Google Scholar 

  145. Motzer, R.J., et al., Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol, 2000. {18}(16): p. 2972–80.

    PubMed  CAS  Google Scholar 

  146. Foon, K., et al., A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma. J Biol Response Mod, 1988. {7}(6): p. 540–5.

    PubMed  CAS  Google Scholar 

  147. De Mulder, P.H., et al., EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. The EORTC Genitourinary Group. Br J Cancer, 1995. {71}(2): p. 371–5.

    PubMed  Google Scholar 

  148. Schalling, M., et al., A role for a new herpes virus (KSHV) in different forms of Kaposi’s sarcoma. Nat Med, 1995. {1}(7): p. 707–8.

    Article  PubMed  CAS  Google Scholar 

  149. Sinkovics, J.G., Kaposi’s sarcoma: its ‘oncogenes’ and growth factors. Crit Rev Oncol Hematol, 1991. {11}(2): p. 87–107.

    Article  PubMed  CAS  Google Scholar 

  150. Ensoli, B., et al., AIDS-Kaposi’s sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. Science, 1989. {243}(4888): p. 223–6.

    Article  PubMed  CAS  Google Scholar 

  151. Folkman, J., Successful treatment of an angiogenic disease. N Engl J Med, 1989. {320}(18): p. 1211–2.

    Article  PubMed  CAS  Google Scholar 

  152. White, C.W., et al., Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med, 1989. {320}(18): p. 1197–200.

    Article  PubMed  CAS  Google Scholar 

  153. Ezekowitz, A., J. Mulliken, and J. Folkman, Interferon alpha therapy of haemangiomas in newborns and infants. Br J Haematol, 1991. {79}(1): p. 67–8.

    Google Scholar 

  154. Real, F.X., H.F. Oettgen, and S.E. Krown, Kaposi’s sarcoma and the acquired immunodeficiency syndrome: treatment with high and low doses of recombinant leukocyte A interferon. J Clin Oncol, 1986. {4}(4): p. 544–51.

    PubMed  CAS  Google Scholar 

  155. Gelmann, E.P., et al., Human lymphoblastoid interferon treatment of Kaposi’s sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters. Am J Med, 1985. {78}(5): p. 737–41.

    Article  PubMed  CAS  Google Scholar 

  156. Groopman, J.E., et al., Recombinant alpha-2 interferon therapy for Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med, 1984. {100}(5): p. 671–6.

    PubMed  CAS  Google Scholar 

  157. Mauss, S. and H. Jablonowski, fficacy, safety, and tolerance of low-dose, long-term interferon-alpha 2b and zidovudine in early-stage AIDS-associated Kaposi’s sarcoma. J Acquir Immune Defic Syndr Hum Retrovirol, 1995. {10}(2): p. 157–62.

    PubMed  CAS  Google Scholar 

  158. Krown, S.E., et al., Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med, 1990. {112}(11): p. 812–21.

    PubMed  CAS  Google Scholar 

  159. Dezube, B.J., L. Pantanowitz, and D.M. Aboulafia, Management of AIDS-related Kaposi sarcoma: advances in target discovery and treatment. AIDS Read, 2004. {14}(5): p. 236–8, 243–4, 251–3.

    Google Scholar 

  160. Jonasch, E. and F.G. Haluska, Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist, 2001. {6}(1): p. 34–55.

    Article  PubMed  CAS  Google Scholar 

  161. Greenberg, D.B., et al., Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes. Cancer, 2000. {v>89}(2): p. 356–62.

    Google Scholar 

  162. Musselman, D.L., et al., Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med, 2001. {344}(13): p. 961–6.

    Article  PubMed  CAS  Google Scholar 

  163. Jonasch, E., et al., Adjuvant high-dose interferon alfa-2b in patients with high-risk melanoma. Cancer J, 2000. {6}(3): p. 139–45.

    PubMed  CAS  Google Scholar 

  164. Lacotte, L., et al., Thrombotic thrombocytopenic purpura during interferon alpha treatment for chronic myelogenous leukemia. Acta Haematol, 2000. {102}(3): p. 160–2.

    Article  PubMed  CAS  Google Scholar 

  165. Ravandi-Kashani, F., et al., Thrombotic microangiopathy associated with interferon therapy for patients with chronic myelogenous leukemia: coincidence or true side effect? Cancer, 1999. {85}(12): p. 2583–8.

    Article  PubMed  CAS  Google Scholar 

  166. Rachmani, R., et al., Thrombotic thrombocytopenic purpura complicating chronic myelogenous leukemia treated with interferon-alpha. A report of two successfully treated patients. Acta Haematol, 1998. {100}(4): p. 204–6.

    Article  PubMed  CAS  Google Scholar 

  167. Iyoda, K., et al., Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C. J Gastroenterol, 1998. {33}(4): p. 588–92.

    Article  PubMed  CAS  Google Scholar 

  168. Gentile, I., et al., Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit. J Interferon Cytokine Res, 2005. {25}(5): p. 283–5.

    Article  PubMed  CAS  Google Scholar 

  169. Braathen, L.R. and P. Stavem, Autoimmune haemolytic anaemia associated with interferon alfa-2a in a patient with mycosis fungoides. BMJ, 1989. {298}(6689): p. 1713.

    Google Scholar 

  170. Pangalis, G.A. and E. Griva, Recombinant alfa-2b-interferon therapy in untreated, stages A and B chronic lymphocytic leukemia. A preliminary report. Cancer, 1988. {61}(5): p. 869–72.

    Article  PubMed  CAS  Google Scholar 

  171. Akard, L.P., et al., Alpha-interferon and immune hemolytic anemia. Ann Intern Med, 1986. {105}(2): p. 306.

    Google Scholar 

  172. Jones, T.H., S. Wadler, and K.H. Hupart, Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha. Semin Oncol, 1998. {25}(1): p. 54–63.

    Google Scholar 

  173. Brudin, L.H., et al., Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. Eur J Nucl Med, 1994. {21}(4): p. 297–305.

    Article  PubMed  CAS  Google Scholar 

  174. Lewis, P.J. and A. Salama, Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med, 1994. {35}(10): p. 1647–9.

    PubMed  CAS  Google Scholar 

  175. Brenard, R., Practical management of patients treated with alpha interferon. Acta Gastroenterol Belg, 1997. {60}(3): p. 211–3.

    PubMed  CAS  Google Scholar 

  176. Dalekos, G.N., et al., A prospective evaluation of dermatological side-effects during alpha-interferon therapy for chronic viral hepatitis. Eur J Gastroenterol Hepatol, 1998. {10}(11): p. 933–9.

    Article  PubMed  CAS  Google Scholar 

  177. Gogas, H., et al., Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med, 2006. {354}(7): p. 709–18.

    Article  PubMed  CAS  Google Scholar 

  178. Waldmann, T.A. and M. Tsudo, Interleukin-2 receptors: biology and therapeutic potentials. Hosp Pract (Off Ed), 1987. {22}(1): p. 77–84, 93–4.

    Google Scholar 

  179. Chan, W.C., et al., Large granular lymphocyte proliferation: an analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents. Blood, 1988. {71}(1): p. 52–8.

    PubMed  CAS  Google Scholar 

  180. Begley, C.G., et al., Human B lymphocytes express the p75 component of the interleukin 2 receptor. Leuk Res, 1990. {14}(3): p. 263–71.

    Article  PubMed  CAS  Google Scholar 

  181. Mingari, M.C., et al., Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells. Nature, 1984. {312}(5995): p. 641–3.

    Article  PubMed  CAS  Google Scholar 

  182. Sakaguchi, S., et al., Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol, 1995. {155}(3): p. 1151–64.

    PubMed  CAS  Google Scholar 

  183. Golgher, D., et al., Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur J Immunol, 2002. {32}(11): p. 3267–75.

    Article  PubMed  CAS  Google Scholar 

  184. Barmeyer, C., et al., The interleukin-2-deficient mouse model. Pathobiology, 2002. {70}(3): p. 139–42.}

    Article  PubMed  CAS  Google Scholar 

  185. Baumgart, D.C., et al., Mechanisms of intestinal epithelial cell injury and colitis in interleukin 2 (IL2)-deficient mice. Cell Immunol, 1998. {187}(1): p. 52–66.

    Article  PubMed  CAS  Google Scholar 

  186. Garrelds, I.M., et al., Interleukin-2-Deficient mice: effect on cytokines and inflammatory cells in chronic colonic disease. Dig Dis Sci, 2002. {47}(3): p. 503–10.

    Article  PubMed  CAS  Google Scholar 

  187. Kung, J.T., D. Beller, and S.T. Ju, Lymphokine regulation of activation-induced apoptosis in T cells of IL-2 and IL-2R beta knockout mice. Cell Immunol, 1998. {185}(2): p. 158–63.

    Article  PubMed  CAS  Google Scholar 

  188. Negrier, S., et al., Interleukin-2 with or without LAK cells in metastatic renal cell carcinoma: a report of a European multicentre study. Eur J Cancer Clin Oncol, 1989. {25}(Suppl 3): p. S21–8.

    Google Scholar 

  189. Topalian, S.L., et al., Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol, 1988. {6}(5): p. 839–53.

    PubMed  CAS  Google Scholar 

  190. Rosenberg, S.A., et al., Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med, 1985. {313}(23): p. 1485–92.

    Article  PubMed  CAS  Google Scholar 

  191. Fisher, R.I., S.A. Rosenberg, and G. Fyfe, Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am, 2000. {6}(Suppl 1): p. S55–7.

    Google Scholar 

  192. Fyfe, G.A., et al., Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy. J Clin Oncol, 1996. {14}(8): p. 2410–1.

    PubMed  CAS  Google Scholar 

  193. Yang, J.C., et al., Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol, 2003. {21}(16): p. 3127–32.

    Article  PubMed  CAS  Google Scholar 

  194. Atzpodien, J., et al., Treatment of metastatic renal cell cancer patients with recombinant subcutaneous human interleukin-2 and interferon-alpha. Ann Oncol, 1990. {1}(5): p. 377–8.

    PubMed  CAS  Google Scholar 

  195. Figlin, R.A., et al., Concomitant administration of recombinant human interleukin-2 and recombinant interferon alfa-2A: an active outpatient regimen in metastatic renal cell carcinoma. J Clin Oncol, 1992. {10}(3): p. 414–21.

    PubMed  CAS  Google Scholar 

  196. Veelken, H., et al., Combination of interleukin-2 and interferon-alpha in renal cell carcinoma and malignant melanoma: a phase II clinical trial. Biotechnol Ther, 1992. {3}(1–2): p. 1–14.

    PubMed  CAS  Google Scholar 

  197. Atzpodien, J., et al., Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol, 2004. {22}(7): p. 1188–94.

    Article  PubMed  CAS  Google Scholar 

  198. McDermott, D.F., et al., Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol, 2005. {23}(1): p. 133–41.

    Article  PubMed  CAS  Google Scholar 

  199. Atkins, M.B., et al., High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am, 2000. {6}(Suppl 1): p. S11–4.

    Google Scholar 

  200. Atkins, M.B., Cytokine-based and biochemotherapy for advanced melanoma. Clin Cancer Res, 2006. {12}(7 Pt 2): p. 2353s–8s.

    Article  PubMed  CAS  Google Scholar 

  201. Rosenberg, S.A., et al., Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med, 1998. {4}(3): p. 321–7.

    Article  PubMed  CAS  Google Scholar 

  202. Rosenberg, S.A., et al., Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J Immunol, 1999. {163}(3): p. 1690–5.

    PubMed  CAS  Google Scholar 

  203. Gollob, J., L. Flaherty, and J. Smith. A Cytokine Working Group (CWG) phase II trial of a modified gp100 melanoma peptide (gp100 (209M)) and high dose interleukin-2 (HD IL-2) administered q3 weeks in patients with stage IV melanoma: limited antitumor activity. Prog Proc Am Soc Clin Oncol, 2001, abstr 1423.

    Google Scholar 

  204. Rosenberg, S.A., et al., Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol, 1989. {7}(12): p. 1863–74.

    PubMed  CAS  Google Scholar 

  205. Kruit, W.H., et al., Dose efficacy study of two schedules of high-dose bolus administration of interleukin 2 and interferon alpha in metastatic melanoma. Br J Cancer, 1996. {74}(6): p. 951–5.

    PubMed  CAS  Google Scholar 

  206. Sparano, J.A., et al., Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. J Clin Oncol, 1993. {11}(10): p. 1969–77.

    PubMed  CAS  Google Scholar 

  207. Feun, L., et al., Cyclosporine A, alpha-lnterferon and interleukin-2 following chemotherapy with BCNU, DTIC, cisplatin, and tamoxifen: a phase II study in advanced melanoma. Cancer Invest, 2005. {23}(1): p. 3–8.

    Article  PubMed  CAS  Google Scholar 

  208. Atkins, M.B., et al., A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Clin Cancer Res, 2002. {8}(10): p. 3075–81.

    PubMed  CAS  Google Scholar 

  209. McDermott, D.F., et al., A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin 2, and interferon alpha-2B in patients with metastatic melanoma. Clin Cancer Res, 2000. {6}(6): p. 2201–8.

    PubMed  CAS  Google Scholar 

  210. Gibbs, P., et al., A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma. Melanoma Res, 2000. {10}(2): p. 171–9.

    PubMed  CAS  Google Scholar 

  211. Johnston, S.R., et al., Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma. Br J Cancer, 1998. {77}(8): p. 1280–6.

    PubMed  CAS  Google Scholar 

  212. Eton, O., et al., Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol, 2002. {20}(8): p. 2045–52.

    Article  PubMed  CAS  Google Scholar 

  213. Hauschild, A., et al., Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG). Br J Cancer, 2001. {84}(8): p. 1036–42.

    Article  PubMed  CAS  Google Scholar 

  214. Rosenberg, S.A., et al., Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol, 1999. {17}(3): p. 968–75.

    PubMed  CAS  Google Scholar 

  215. Atkins, M.B., et al., A prospective randomized phase III trial of concurrent biochemotherapy (BCT) with cisplatin, vinblastine, dacarbazine (CVD), IL-2 and interferon alpha-2b (IFN) versus CVD alone in patients with metastatic melanoma (E3695): An ECOG-coordinated intergroup trial. ASCO Annual Meeting Proceedings, 2003: p. 2847.

    Google Scholar 

  216. O’Day, S.J., et al., Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy. Clin Cancer Res, 2002. {8}(9): p. 2775–81.

    PubMed  CAS  Google Scholar 

  217. O’Day, S., et al., A phase II multi-center trial of maintenance biotherapy (MBT) after induction concurrent biochemotherapy (BCT) for patients (Pts) with metastatic melanoma (MM). ASCO Annual Meetings Proceedings, 2005. {23}(Suppl 16): p. 7503.

    Google Scholar 

  218. Schwartz, R.N., L. Stover, and J. Dutcher, Managing toxicities of high-dose interleukin-2. Oncology, 2002. {16}(11 Suppl 13): p. 11–20.

    PubMed  Google Scholar 

  219. Klempner, M.S., et al., An acquired chemotactic defect in neutrophils from patients receiving interleukin-2 immunotherapy. N Engl J Med, 1990. {322}(14): p. 959–65.

    Article  PubMed  CAS  Google Scholar 

  220. Tilg, H., et al., Induction of circulating soluble tumour necrosis factor receptor and interleukin 1 receptor antagonist following interleukin 1 alpha infusion in humans. Cytokine, 1994. {6}(2): p. 215–9.

    Article  PubMed  CAS  Google Scholar 

  221. Tilg, H., et al., Induction of circulating and erythrocyte-bound IL-8 by IL-2 immunotherapy and suppression of its in vitro production by IL-1 receptor antagonist and soluble tumor necrosis factor receptor (p75) chimera. J Immunol, 1993. {151}(6): p. 3299–307.

    PubMed  CAS  Google Scholar 

  222. Margolin, K., et al., Prospective randomized trial of lisofylline for the prevention of toxicities of high-dose interleukin 2 therapy in advanced renal cancer and malignant melanoma. Clin Cancer Res, 1997. {3}(4): p. 565–72.

    PubMed  CAS  Google Scholar 

  223. Du Bois, J.S., et al., Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma. J Clin Oncol, 1997. {15}(3): p. 1052–62.

    PubMed  Google Scholar 

  224. Atkins, M.B., et al., A phase I study of CNI-1493, an inhibitor of cytokine release, in combination with high-dose interleukin-2 in patients with renal cancer and melanoma. Clin Cancer Res, 2001. {7}(3): p. 486–92.

    PubMed  CAS  Google Scholar 

  225. Kilbourn, R.G., et al., Strategies to reduce side effects of interleukin-2: evaluation of the antihypotensive agent NG-monomethyl-L-arginine. Cancer J Sci Am, 2000. {6}(Suppl 1): p. S21–30.

    Google Scholar 

  226. Kilbourn, R.G., et al., NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, reverses interleukin-2-induced hypotension. Crit Care Med, 1995. {23}(6): p. 1018–24.

    Article  PubMed  CAS  Google Scholar 

  227. Trinchieri, G., Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol, 2003. {3}(2): p. 133–46.

    Article  PubMed  CAS  Google Scholar 

  228. Bermudez, L.E., M. Wu, and L.S. Young, Interleukin-12-stimulated natural killer cells can activate human macrophages to inhibit growth of Mycobacterium avium. Infect Immun, 1995. {63}(10): p. 4099–104.

    PubMed  CAS  Google Scholar 

  229. Kaufmann, S.H., C.H. Ladel, and I.E. Flesch, T cells and cytokines in intracellular bacterial infections: experiences with Mycobacterium bovis BCG. Ciba Found Symp, 1995. {195}: p. 123–32; discussion 132–6.

    PubMed  CAS  Google Scholar 

  230. Reis e Sousa, C., et al., In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J Exp Med, 1997. {186}(11): p. 1819–29.

    Article  PubMed  CAS  Google Scholar 

  231. Coutelier, J.P., J. Van Broeck, and S.F. Wolf, Interleukin-12 gene expression after viral infection in the mouse. J Virol, 1995. {69}(3): p. 1955–8.

    PubMed  CAS  Google Scholar 

  232. Kobayashi, M., et al., Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med, 1989. {170}(3): p. 827–45.}

    Article  PubMed  CAS  Google Scholar 

  233. Kubin, M., M. Kamoun, and G. Trinchieri, Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells. J Exp Med, 1994. {180}(1): p. 211–22.

    Article  PubMed  CAS  Google Scholar 

  234. Perussia, B., et al., Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells. J Immunol, 1992. {149}(11): p. 3495–502.

    PubMed  CAS  Google Scholar 

  235. Manetti, R., et al., Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med, 1993. {177}(4): p. 1199–204.

    Article  PubMed  CAS  Google Scholar 

  236. Satoh, Y., et al., Local administration of IL-12-transfected dendritic cells induces antitumor immune responses to colon adenocarcinoma in the liver in mice. J Exp Ther Oncol, 2002. {2}(6): p. 337–49.

    Article  PubMed  CAS  Google Scholar 

  237. Mazzolini, G., et al., Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12. Cancer Gene Ther, 1999. {6}(6): p. 514–22.

    Article  PubMed  CAS  Google Scholar 

  238. Gao, J.Q., et al., A single intratumoral injection of a fiber-mutant adenoviral vector encoding interleukin 12 induces remarkable anti-tumor and anti-metastatic activity in mice with Meth-A fibrosarcoma. Biochem Biophys Res Commun, 2005. {328}(4): p. 1043–50.

    Article  PubMed  CAS  Google Scholar 

  239. Bramson, J.L., et al., Direct intratumoral injection of an adenovirus expressing interleukin-12 induces regression and long-lasting immunity that is associated with highly localized expression of interleukin-12. Hum Gene Ther, 1996. {7}(16): p. 1995–2002.

    Google Scholar 

  240. Kodama, T., et al., Perforin-dependent NK cell cytotoxicity is sufficient for anti-metastatic effect of IL-12. Eur J Immunol, 1999. {29}(4): p. 1390–6.

    Article  PubMed  CAS  Google Scholar 

  241. Smyth, M.J., et al., NKG2D recognition and perforin effector function mediate effective cytokine immunotherapy of cancer. J Exp Med, 2004. {200}(10): p. 1325–35.

    Article  PubMed  CAS  Google Scholar 

  242. Kawamura, T., et al., Critical role of NK1+ T cells in IL-12-induced immune responses in vivo. J Immunol, 1998. {160}(1): p. 16–9.

    PubMed  CAS  Google Scholar 

  243. Boggio, K., et al., Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. J Exp Med, 1998. {188}(3): p. 589–96.

    Article  PubMed  CAS  Google Scholar 

  244. Gollob, J.A., et al., Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res, 2000. {6}(5): p. 1678–92.

    PubMed  CAS  Google Scholar 

  245. Okamura, H., et al., Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature, 1995. {378}(6552): p. 88–91.

    Article  PubMed  CAS  Google Scholar 

  246. Micallef, M.J., et al., Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production. Eur J Immunol, 1996. {26}(7): p. 1647–51.

    Article  PubMed  CAS  Google Scholar 

  247. Tsutsui, H., et al., IL-18 accounts for both TNF-alpha- and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice. J Immunol, 1997. {159}(8): p. 3961–7.

    PubMed  CAS  Google Scholar 

  248. Tomura, M., et al., A critical role for IL-18 in the proliferation and activation of NK1.1+ CD3- cells. J Immunol, 1998. {160}(10): p. 4738–46.

    PubMed  CAS  Google Scholar 

  249. Hunter, C.A., et al., Comparison of the effects of interleukin-1 alpha, interleukin-1 beta and interferon-gamma-inducing factor on the production of interferon-gamma by natural killer. Eur J Immunol, 1997. {27}(11): p. 2787–92.

    Article  PubMed  CAS  Google Scholar 

  250. Hoshino, K., et al., The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function. J Exp Med, 1999. {190}(10): p. 1541–8.

    Article  PubMed  CAS  Google Scholar 

  251. Tsutsui, H., et al., IFN-gamma-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J Immunol, 1996. {157}(9): p. 3967–73.

    PubMed  CAS  Google Scholar 

  252. Dao, T., et al., Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell Immunol, 1996. {173}(2): p. 230–5.

    Article  PubMed  CAS  Google Scholar 

  253. Park, C.C., et al., Evidence of IL-18 as a novel angiogenic mediator. J Immunol, 2001. {167}(3): p. 1644–53.

    PubMed  CAS  Google Scholar 

  254. Coughlin, C.M., et al., Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest, 1998. {101}(6): p. 1441–52.

    Article  PubMed  CAS  Google Scholar 

  255. Paulukat, J., et al., Expression and release of IL-18 binding protein in response to IFN-gamma. J Immunol, 2001. {167}(12): p. 7038–43.

    PubMed  CAS  Google Scholar 

  256. Novick, D., et al., Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity, 1999. {10}(1): p. 127–36.

    Article  PubMed  CAS  Google Scholar 

  257. Robertson, M.J., et al., Phase I study of recombinant human IL-18 (rhIL-18) administered as five daily intravenous infusions every 28 days in patients with solid tumors. ASCO Annual Meeting Proceedings, 2005: p. 2513.

    Google Scholar 

  258. Koch, K.M., et al., PK and PD of recombinant human IL-18 (rhIL-18) administered IV in repeated cycles to patients with solid tumors. ASCO Annual Meeting Proceedings, 2005: p. 2535.

    Google Scholar 

  259. Lewis, N., et al., Phase I dose escalation study to assess tolerability and pharmacokinetics of recombinant human IL-18 (rhIL-18) administered as fourteen daily subcutaneous injections in patients with solid tumors. ASCO Annual Meeting Proceedings, 2004: p. 2591.

    Google Scholar 

  260. Parrish-Novak, J., et al., Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature, 2000. {408}(6808): p. 57–63.

    Article  PubMed  CAS  Google Scholar 

  261. Brandt, K., et al., Interleukin-21 inhibits dendritic cell activation and maturation. Blood, 2003. {102}(12): p. 4090–8.

    Article  PubMed  CAS  Google Scholar 

  262. Suto, A., et al., Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells. Blood, 2002. {100}(13): p. 4565–73.

    Article  PubMed  CAS  Google Scholar 

  263. Pene, J., et al., Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. J Immunol, 2004. {172}(9): p. 5154–7.

    PubMed  CAS  Google Scholar 

  264. Habib, T., A. Nelson, and K. Kaushansky, IL-21: a novel IL-2-family lymphokine that modulates B, T, and natural killer cell responses. J Allergy Clin Immunol, 2003. {112}(6): p. 1033–45.

    Article  PubMed  CAS  Google Scholar 

  265. Wang, G., et al., In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res, 2003. {63}(24): p. 9016–22.

    PubMed  CAS  Google Scholar 

  266. Ugai, S., et al., Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects. Cancer Gene Ther, 2003. {10}(10): p. 771–8.

    Article  PubMed  CAS  Google Scholar 

  267. Ugai, S., et al., Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts. Cancer Gene Ther, 2003. {10}(3): p. 187–92.

    Article  PubMed  CAS  Google Scholar 

  268. Takaki, R., et al., IL-21 enhances tumor rejection through a NKG2D-dependent mechanism. J Immunol, 2005. {175}(4): p. 2167–73.

    PubMed  CAS  Google Scholar 

  269. Moroz, A., et al., IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21. J Immunol, 2004. {173}(2): p. 900–9.

    PubMed  CAS  Google Scholar 

  270. Ma, H.L., et al., IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma. J Immunol, 2003. {171}(2): p. 608–15.

    PubMed  CAS  Google Scholar 

  271. Kishida, T., et al., Interleukin (IL)-21 and IL-15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastatic lymphoma. Mol Ther, 2003. {8}(4): p. 552–8.

    Article  PubMed  CAS  Google Scholar 

  272. Curti, B.D., et al., Preliminary tolerability and anti-tumor activity of intravenous recombinant human Interleukin-21 (IL-21) in patients with metastatic melanoma and metastatic renal cell carcinoma. ASCO Annual Meeting Proceedings, 2005: p. 2502.

    Google Scholar 

  273. Dranoff, G., et al., Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA, 1993. {90}(8): p. 3539–43.

    Article  PubMed  CAS  Google Scholar 

  274. Grabstein, K.H., et al., Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science, 1986. {232}(4749): p. 506–8.

    Article  PubMed  CAS  Google Scholar 

  275. Yamasaki, S., et al., Presentation of synthetic peptide antigen encoded by the MAGE-1 gene by granulocyte/macrophage-colony-stimulating-factor-cultured macrophages from HLA-A1 melanoma patients. Cancer Immunol Immunother, 1995. {40}(4): p. 268–71.

    Article  PubMed  CAS  Google Scholar 

  276. Hanada, K., R. Tsunoda, and H. Hamada, GM-CSF-induced in vivo expansion of splenic dendritic cells and their strong costimulation activity. J Leukoc Biol, 1996. {60}(2): p. 181–90.

    PubMed  CAS  Google Scholar 

  277. Armstrong, C.A., et al., Antitumor effects of granulocyte-macrophage colony-stimulating factor production by melanoma cells. Cancer Res, 1996. {56}(9): p. 2191–8.

    PubMed  CAS  Google Scholar 

  278. Mach, N., et al., Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res, 2000. {60}(12): p. 3239–46.

    PubMed  CAS  Google Scholar 

  279. Hu, H.M., et al., Divergent roles for CD4+ T cells in the priming and effector/memory phases of adoptive immunotherapy. J Immunol, 2000. {165}(8): p. 4246–53.

    PubMed  CAS  Google Scholar 

  280. Ridolfi, L. and R. Ridolfi, Preliminary experiences of intralesional immunotherapy in cutaneous metastatic melanoma. Hepatogastroenterology, 2002. {49}(44): p. 335–9.

    PubMed  CAS  Google Scholar 

  281. Vaquerano, J.E., et al., Regression of in-transit melanoma of the scalp with intralesional recombinant human granulocyte-macrophage colony-stimulating factor. Arch Dermatol, 1999. {135}(10): p. 1276–7.

    Article  PubMed  CAS  Google Scholar 

  282. Si, Z., P. Hersey, and A.S. Coates, Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF. Melanoma Res, 1996. {6}(3): p. 247–55.

    Article  PubMed  CAS  Google Scholar 

  283. Dranoff, G., GM-CSF-secreting melanoma vaccines. Oncogene, 2003. {22}(20): p. 3188–92.

    Article  PubMed  CAS  Google Scholar 

  284. Spitler, L.E., et al., Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol, 2000. {18}(8): p. 1614–21.

    PubMed  CAS  Google Scholar 

  285. Dunn, G.P., L.J. Old, and R.D. Schreiber, The immunobiology of cancer immunosurveillance and immunoediting. Immunity, 2004. {21}(2): p. 137–48.

    Article  PubMed  CAS  Google Scholar 

  286. Rivoltini, L., et al., Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunol Rev, 2002. {188}: p. 97–113.

    Article  PubMed  CAS  Google Scholar 

  287. De Paola, F., et al., Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2. Br J Cancer, 2003. {88}(2): p. 320–6.

    Article  PubMed  CAS  Google Scholar 

  288. Bukowski, R.M., et al., Signal transduction abnormalities in T lymphocytes from patients with advanced renal carcinoma: clinical relevance and effects of cytokine therapy. Clin Cancer Res, 1998. {4}(10): p. 2337–47.

    PubMed  CAS  Google Scholar 

  289. Piancatelli, D., et al., Local expression of cytokines in human colorectal carcinoma: evidence of specific interleukin-6 gene expression. J Immunother, 1999. {22}(1): p. 25–32.

    Article  PubMed  CAS  Google Scholar 

  290. Lissoni, P., et al., Relation between macrophage and T helper-2 lymphocyte functions in human neoplasms: neopterin, interleukin-10 and interleukin-6 blood levels in early or advanced solid tumors. J Biol Regul Homeost Agents, 1995. {9}(4): p. 146–9.

    PubMed  CAS  Google Scholar 

  291. Chen, C.K., et al., T lymphocytes and cytokine production in ascitic fluid of ovarian malignancies. J Formos Med Assoc, 1999. {98}(1): p. 24–30.

    PubMed  CAS  Google Scholar 

  292. Nemunaitis, J., et al., Comparison of serum interleukin-10 (IL-10) levels between normal volunteers and patients with advanced melanoma. Cancer Invest, 2001. {19}(3): p. 239–47.

    Article  PubMed  CAS  Google Scholar 

  293. Chen, Q., et al., Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma. Int J Cancer, 1994. {56}(5): p. 755–60.

    Article  PubMed  CAS  Google Scholar 

  294. Kim, R., et al., Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res, 2006. {66}(11): p. 5527–36.

    Article  PubMed  CAS  Google Scholar 

  295. Smyth, M.J. and D.I. Godfrey, NKT cells and tumor immunity–a double-edged sword. Nat Immunol, 2000. {1}(6): p. 459–60.

    Article  PubMed  CAS  Google Scholar 

  296. Yanagisawa, K., et al., Impaired proliferative response of V alpha 24 NKT cells from cancer patients against alpha-galactosylceramide. J Immunol, 2002. {168}(12): p. 6494–9.

    PubMed  CAS  Google Scholar 

  297. van der Vliet, H.J., et al., Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells. Cancer Res, 2003. {63}(14): p. 4101–6.

    PubMed  Google Scholar 

  298. Tahir, S.M., et al., Loss of IFN-gamma production by invariant NK T cells in advanced cancer. J Immunol, 2001. {167}(7): p. 4046–50.

    PubMed  CAS  Google Scholar 

  299. Dhodapkar, M.V., et al., A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma. J Exp Med, 2003. {197}(12): p. 1667–76.

    Article  PubMed  CAS  Google Scholar 

  300. Viguier, M., et al., Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol, 2004. {173}(2): p. 1444–53.

    PubMed  CAS  Google Scholar 

  301. Marshall, N.A., et al., Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood, 2004. {103}(5): p. 1755–62.

    Article  PubMed  CAS  Google Scholar 

  302. Akasaki, Y., et al., Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol, 2004. {173}(7): p. 4352–9.

    PubMed  CAS  Google Scholar 

  303. Cesana, G.C., et al., Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol, 2006. {24}(7): p. 1169–77.

    Article  PubMed  CAS  Google Scholar 

  304. Tomura, M., et al., A novel function of Valpha14+CD4+NKT cells: stimulation of IL-12 production by antigen-presenting cells in the innate immune system. J Immunol, 1999. {163}(1): p. 93–101.

    PubMed  CAS  Google Scholar 

  305. Kitamura, H., et al., The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)- 12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med, 1999. {189}(7): p. 1121–8.

    Article  PubMed  CAS  Google Scholar 

  306. Chang, D.H., et al., Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med, 2005. {201}(9): p. 1503–17.

    Article  PubMed  CAS  Google Scholar 

  307. Fujii, S., et al., Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol, 2002. {3}(9): p. 867–74.

    Article  PubMed  CAS  Google Scholar 

  308. Barnett, B., et al. Depleting CD4+ CD25+ Regulatory T-cells improves immunity in cancer-bearing patients. Proceedings of AACR, 2004.

    Google Scholar 

  309. Vieweg, J., Z. Su, and J. Dannuli. Enhancement of antitumor immunity following depletion of CD+CD25+ regulatory T-cells. Proceedings of ASCO, 2004.

    Google Scholar 

  310. Dudley, M.E., et al., A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother, 2002. {25}(3): p. 243–51.

    Article  PubMed  CAS  Google Scholar 

  311. Dudley, M.E., et al., Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science, 2002. {298}(5594): p. 850–4.

    Article  PubMed  CAS  Google Scholar 

  312. Phan, G.Q., et al., Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA, 2003. {100}(14): p. 8372–7.

    Article  PubMed  CAS  Google Scholar 

  313. Reuben, J.M., et al., Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma. Cancer, 2006. {106}(11): p. 2437–44.

    Article  PubMed  CAS  Google Scholar 

  314. Ribas, A., et al., Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol, 2005. {23}(35): p. 8968–77.

    Article  PubMed  CAS  Google Scholar 

  315. Maker, A.V., et al., Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol, 2005. {12}(12): p. 1005–16.

    Article  PubMed  Google Scholar 

  316. Upton, M.P., et al., Histologic predictors of renal cell carcinoma (RCC) response to interleukin-2-based therapy. ASCO Annual Meeting Proceedings, 2004: p. 3420.

    Google Scholar 

  317. Bui, M.H., et al., Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clin Cancer Res, 2004. {9}(2): p. 802–11.

    Google Scholar 

  318. Atkins, M., et al., Carbonic Anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy. ASCO Annual Meeting Proceedings, 2004. p. 4512.

    Google Scholar 

  319. Scheibenbogen, C., et al., HLA class I alleles and responsiveness of melanoma to immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Melanoma Res, 1994. {4}(3): p. 191–4.

    Article  PubMed  CAS  Google Scholar 

  320. Tartour, E., et al., Predictors of clinical response to interleukin-2–based immunotherapy in melanoma patients: a French multiinstitutional study. J Clin Oncol, 1996. {14}(5): p. 1697–703.

    PubMed  CAS  Google Scholar 

  321. Liu, D., et al., Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. Clin Cancer Res, 2005. {11}(3): p. 1237–46.

    PubMed  CAS  Google Scholar 

  322. Garcia-Hernandez, M.L., et al., Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation. Immunology, 2002. {105}(2): p. 231–43.

    Article  PubMed  CAS  Google Scholar 

  323. Huang, S., et al., Interleukin 10 suppresses tumor growth and metastasis of human melanoma cells: potential inhibition of angiogenesis. Clin Cancer Res, 1996. 2(12): p. 1969–79.

    PubMed  CAS  Google Scholar 

  324. Howell, W.M., et al., IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma. Genes Immun, 2001. {2}(1): p. 25–31.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Henry B. Koon MD
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  2. Michael B.Atkins MD
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Editors and Affiliations

  1. Division of Surgical Oncology, Columbia University, New York, NY

    Howard L. Kaufman

  2. Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College Cornell University, New York, NY

    Scott Wadler

  3. Boston University Medical Campus Boston University School of Medicine, Boston, MA

    Karen Antman

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Koon, H.B., B.Atkins, M. (2008). Cytokine-Based Therapy for Cancer. In: Kaufman, H.L., Wadler, S., Antman, K. (eds) Molecular Targeting in Oncology. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-337-0_20

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  • DOI: https://doi.org/10.1007/978-1-59745-337-0_20

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