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Therapeutic applications of cytokines for immunostimulation and immunosuppression: An update

  • Chapter
Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques

Abstract

As we indicated in an early review on this subject [1], the clinical use of proteins as drugs is not a new practice. What is new is the ability to produce almost limitless quantities of many clinically relevant proteins, and our depth of understanding of the mechanisms underlying their physiologic function. Unfortunately, neither of these aspects guarantees a successful transition from the laboratory to a meaningful clinical application. Despite being endogenous mediators of cell function, systemic administration of cytokines resulting in supraphysiologic levels often leads to toxicity [2]. Nevertheless, as predicted in our previous discussion, activity over the past four years in the field of clinical applications of cytokines and interleukins has been of sufficient volume to preclude a comprehensive overview in a single chapter. For some cytokines, such as the interferons and IL-2, a clinical role has been established and much of the recent work has focused on refining dosages, routes of administration, and schedules as well as investigations of combining these agents together or with other drugs with the goal of improving efficacy. In other cases, for example TNF and IL-1, despite being among the first cytokines to be characterized, clearly defined successful therapeutic applications remain elusive. For more recently identified cytokines such as IL-12 and IL-15, clinical trials remain in the earliest stages.

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References

  1. B. Leeand T L. Ciardelli: Clinical applications of cytokines for immunostimulation and immunosuppression. Prog, in Drug Res. 39, 167 (1992).

    CAS  Google Scholar 

  2. T. Vail and J. Descotes: Immune-mediated side-effects of cytokines in humans. Toxicology 105, 31 (1995).

    Article  Google Scholar 

  3. M.A.S. Moore: Hematopoietic reconstruction: New approaches. Clin. Cancer Res. 1, 3 (1995).

    PubMed  CAS  Google Scholar 

  4. M.J. George: The present and future of hematopoietic cytokines in clinical practice. Stem Cells (Dayt) 12 S1, 249 (1994).

    Article  Google Scholar 

  5. P.J.Quesenberry: Biotherapy in hematology:The next decade. Rev. Invest. Clin. Apr. S., 8 (1994).

    Google Scholar 

  6. F. Takaku: Clinical application of cytokines for cancer treatment. Oncology 51, 123 (1994).

    Article  PubMed  CAS  Google Scholar 

  7. R. Mertelsmann: Hematopoietic cytokines: from biology and pathophysiology to clinical application. Leukemia7 S2, 168 (1993).

    Google Scholar 

  8. G.M. Clore, P.T. Wingfield and A.M. Gronenborn: High-resolution three-dimensional structure of interleukin 1 beta in solution by three- and four-dimensional nuclear magnetic resonance spectroscopy. Biochemistry 30, 2315 (1991).

    Article  PubMed  CAS  Google Scholar 

  9. K. Ye, K.C. Koch, B.D. Clark and CA. Dinarello: Interleukin-1 down-regulates gene and surface expression of interleukin-1 receptor type I by destabilizing its mRNA whereas interleukin-2 increases its expression. Immunology 75, 427 (1992).

    PubMed  CAS  Google Scholar 

  10. J. Smith, W. Urba, R. Steis, J. Janik et al.: Interleukin-1 alpha: Results of a phase one toxicity and immunomodulatory trial. Am. Soc. Clin. Oncol. 9, 717 (1990).

    Google Scholar 

  11. CA. Haworth, N.M. Ravindir and M. Feldman, Prospects for cytokines in human immunotherapy. The cytokine handbook (Academic Press, 1994).

    Google Scholar 

  12. C.A. Dinarello and S.M. Wolff: The role of interleukin-1 in disease. N. Engl. J. Med. 328, 106 (1993).

    Article  PubMed  CAS  Google Scholar 

  13. C.A. Dinarello: The interleukin-1 family:10 years of discovery. FASEB J. 8, 1314 (1994).

    PubMed  CAS  Google Scholar 

  14. C.A. Dinarello: Interleukin-1. Adv. in Pharm. 25, 21 (1994).

    Article  CAS  Google Scholar 

  15. B.G. Redman, Y. Abubakr, T. Chou et al: Phase II trial of recombinant interleukin-1 beta in patients with metastatic renal cell carcinoma. J. Immunother. Emphasis Tumor Immunol. 16, 211 (1994).

    PubMed  CAS  Google Scholar 

  16. PL. Triozzi, J.A.Kim, E.W Martin et al: Phase II trial of escalating doses of interleukin-lß in combination with a fixed dose of interleukin-2. J. Clin. Oncol. 13, 482 (1995).

    CAS  Google Scholar 

  17. J. Crown, A. Jakubowski and J. Gabrilove: Interleukin-1: biological effects in human hematopoiesis. Leuk. Lymphoma 9, 433 (1993).

    Article  PubMed  CAS  Google Scholar 

  18. J.W Smith 2nd, WJ.Urba, B.D.Curti et al.: The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies. J. Clin.Oncol.10, 1141(1992).

    PubMed  Google Scholar 

  19. D. Weisdorf, E. Katsanis, C. Verfaillie et al.: Interleukin-1 alpha administered after autologous transplantation. Blood 84, 2044 (1994).

    PubMed  CAS  Google Scholar 

  20. C.A. Dinarello: Blocking interleukin-1 receptors. Int. J. Clin. Lab. Res.24, 61 (1994).

    Article  PubMed  CAS  Google Scholar 

  21. W.P. Arend: Interleukin-1 antagonism in inflammatory disease. Lancet 16, 155 (1993).

    Article  Google Scholar 

  22. P. Ghiara, D. Armellini, G. Scapigliati et al.: Biological role of the IL-1 receptor type II as defined by monoclonal antibody. Cytokine 3, 1423 (1991).

    Article  Google Scholar 

  23. C.A. Jacobs, M.P. Beekman, K. Mohler et al.: Pharmacokinetic parameters and biodistribution of soluble cytokine receptors. Internat. Rev. Exp. Path. 34, 123 (1993).

    Google Scholar 

  24. S.P Eisenberg, R.J. Evans, W.P.Arend et al.: Primary structure and functional expression from complementary DNA of a human interleukin-1 antagonist. Nature 25, 341 (1990).

    Article  Google Scholar 

  25. C.H. Hannum, C.J. Wilcox, WP. Arend et al.: Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature 343, 336 (1990).

    Article  PubMed  CAS  Google Scholar 

  26. E.V. Granowitz, R. Porat, J.W. Mier et al.: Pharmacokinetics, safety, and immuno-modulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans. Cytokine 4, 353 (1992).

    Article  PubMed  CAS  Google Scholar 

  27. M.D. Mitchell, S.S. Edwin, R.M. Silver and R.J. Romero: Potential agonist action of the interleukin-1 receptor antagonist protein: implications for the treatment of women. J. Clin. Endocrin. Metab. 76, 1386 (1993).

    Article  CAS  Google Scholar 

  28. J.H. Antin, H.J. Weinstein, E.C. Guinan et al.: Recombinant human interleukin-1 receptor antagonist in the treatment of steroid resistant graft-versus-host disease. Blood 84, 1342 (1994).

    PubMed  CAS  Google Scholar 

  29. E. Abraham and T.A. Raffin: Sepsis Therapy Trial. JAMA 271, 1876 (1994).

    CAS  Google Scholar 

  30. C.J. Fisher, J.A. Dhainaut, S.M. Opal et al.: Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome. JAMA 271, 1836 (1994).

    Article  PubMed  Google Scholar 

  31. S.A. Greenfeld, P. Nunes, L. Kwee et al.: Molecular cloning and characterization of a second subunit of the interleukin-1 receptor. J. Biol. Chem. 270, 13757 (1995).

    Article  Google Scholar 

  32. K. A. Smith: Interleukin-2: Inception, impact and implications. Science 240, 1169 (1988).

    Article  PubMed  CAS  Google Scholar 

  33. Y. Minami, T. Kono, T. Miyazaki andT.Taniguchi:The IL-2 receptor complex. Annu. Rev. Immunol. 11, 245 (1993).

    Google Scholar 

  34. T. Taniguchi and Y. Minami: The IL-2/IL-2 receptor system: a current overview. Cell 73, 5 (1993).

    Article  PubMed  CAS  Google Scholar 

  35. J.N. Ihle: Cytokine receptor signalling. Nature 377, 591 (1995).

    CAS  Google Scholar 

  36. S.M. Russell, J.A. Johnston, M. Noguchi et al.: Interaction of IL-2Rß and γc Chains with Jakl and Jak3: Implications for XSCID and XCID. Science 266, 1042 (1994).

    Article  PubMed  CAS  Google Scholar 

  37. B. A. Witthuhn, O. Silvennoinen, O. Miura et al: Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 370, 153 (1994).

    Article  PubMed  CAS  Google Scholar 

  38. T. Miyazaki, A. Kawahara, H. Fujii et al.: Functional Activation of Jakl and Jak3 by Selective Association with IL-2 Receptor Subunits. Science 266, 1045 (1994).

    Article  PubMed  CAS  Google Scholar 

  39. N. Stahl and G.D. Yancopoulos: The Alphas, Betas, and Kinases of Cytokine Receptor Complexes. Cell 74, 587 (1993).

    Article  PubMed  CAS  Google Scholar 

  40. S.M. Gorsch and M.S.Ernstoff: Management of Metastatic Renal Cell Carcinoma: Chemotherapy, Hormonal Therapy and Interferons. In: Comprehensive Textbook of Genitourinary Oncology. N.J.Vogelzang, PT.Scardino,W.U.Shipleyand D.S.Coffey (eds). Williams & Wilkins, Baltimore (1996).

    Google Scholar 

  41. J.K. Bruton and J.M. Koeller: Recombinant interleukin-2. Pharmacotherapy 14, 635 (1994).

    PubMed  CAS  Google Scholar 

  42. M.H. Oppenheim and M.TLotze: Interleukin-2: Solid tumor therapy. Oncology 51, 154 (1994).

    Article  PubMed  CAS  Google Scholar 

  43. D.R. Parkinson and M. Sznol: High-dose interleukin-2 in the therapy of metastatic renal-cell carcinoma. Seminars in Oncology 22, 61 (1995).

    PubMed  CAS  Google Scholar 

  44. S.S. Taneja, W. Pierce, R. Figlin and A. Belldegrun: Immunotherapy for renal cell carcinoma: the era of interleukin-2-based treatment. Urology 45, 911 (1995).

    Article  PubMed  CAS  Google Scholar 

  45. L.T. Vlasveld and E.M. Rankin: Recombinant interleukin-2 in cancer: basic and clinical aspects. Cancer Treatment Reviews 20,275 (1994).

    Article  PubMed  CAS  Google Scholar 

  46. J. Wagstaff, J.W. Baars, G.-J. Wolbink et al.: Renal cell carcinoma and interleukin-2: A review. Eur. J. Cancer 31 A, 401 (1995).

    Article  Google Scholar 

  47. C. Garbe: Perspectives of cytokine treatment in malignant skin tumors. Recent Results Cancer Res. 139, 349 (1995).

    PubMed  CAS  Google Scholar 

  48. R. Whittington and D. Faulds: Interleukin-2. a review of its pharmacological properties and therapeutic use in patients with cancer. Drugs 46, 446 (1993).

    Article  PubMed  CAS  Google Scholar 

  49. S.A. Rosenberg, M.T. Lotze, L.M. Muul et al.: Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant inter-leukin-2 in patients with metastatic cancer. N. Eng. J. Med. 313, 1485 (1985).

    Article  CAS  Google Scholar 

  50. J.R. Ortaldo, A. Mason and R. Overton: Lymphokine activated killer (LAK) cells: analysis of progenitors and effectors. J. Exp. Med. 164, 1193 (1986).

    Article  PubMed  CAS  Google Scholar 

  51. T. Nakarai, M.J. Robertson, M. Streuli et al.: Interleukin 2 Receptor γ Chain Expression on Resting and Activated Lymphoid Cells. J. Exp. Med. 180, 241 (1994).

    Article  PubMed  CAS  Google Scholar 

  52. M. Caligiuri, A. Zmuidzinas, T.J. Manley et al.: Functional Consequences of Interleukin-2 Receptor Expression on Resting Human Lymphocytes. J. Exp. Med. 171, 1509 (1990).

    Article  PubMed  CAS  Google Scholar 

  53. S.A. Rosenberg, M.T. Lotze, J.C. Yang et al.: Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J. Natl. Cancer Inst. 85, 622 (1993).

    Article  PubMed  CAS  Google Scholar 

  54. M.J. Koretz, D.H. Lawson, M. York et al.: Randomized study of interleukin-2 (IL-2) vs IL-2 plus lymphokine-activated killer cells for the treatment of melanoma and renal cell cancer. Arch. Surg. 126, 898 (1991).

    PubMed  CAS  Google Scholar 

  55. P.A. Palmer, J. Vinke, P. Evers et al.: Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine activated killer cells for the treatment of advanced renal cell carcinoma. Eur. J. Cancer 28A, 1038 (1992).

    Article  PubMed  CAS  Google Scholar 

  56. S. Legha, M.A. Gianan, C. Plager et al.: Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma. Cancer 77, 89 (1996).

    Article  PubMed  CAS  Google Scholar 

  57. TM.Law, R.J.Motzer, M.Madhu et al.: Phase III randomized trial of interleukin-2 with or without lymphokine activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer76, 824(1995).

    Article  PubMed  CAS  Google Scholar 

  58. B. Fisher, B.S. Packard, E.J. Read et al.: Tumor localization of adoptively transferred Indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J. Clin. Oncol. 7, 250 (1989).

    PubMed  CAS  Google Scholar 

  59. CD.Platsoucas: Human autologous tumor-specific T-cells in malignant melanoma. Metastasis Rev. 10, 151(1991).

    Article  CAS  Google Scholar 

  60. W.C. Pierce, A. Belldegrun and R.A. Figlin: Cellular therapy: scientific rationale and clinical results in the treatment of metastatic renal cell carcinoma. Semin. Oncol. 22, 74 (1995).

    PubMed  CAS  Google Scholar 

  61. J.A. Thompson, M.C. Benyunes, J.A. Bianco and A. Fefer: Treatment with pento-xifylline and ciprofloxacin reduces the toxicity of high-dose interleukin-2 and lymphokine-activated killer cells. Semin. Oncol. 20, 46 (1993).

    PubMed  CAS  Google Scholar 

  62. J.A. Anderson , T.M.Woodcock, J.I.Harty et al.: The effects of pentoxifylline on interleukin-2 toxicity in patients with metastatic renal cell carcinoma. Eur. J. Cancer 31 A, 714 (1995).

    Article  Google Scholar 

  63. M.R. Albertini, J.A. Sosman, J.A. Hank et al.: The influence of autologous lymphokine activated killer cell infusions on the toxicity and antitumor effect of repetitive cycles of interleukin-2. Cancer 66, 2457 (1990).

    Article  PubMed  CAS  Google Scholar 

  64. J.C. Yang, S.L. Topalian, D. Parkinson et al.: Randomized comparison of high-dose and low-dose intravenous interleukin-2 for therapy of metastatic renal cell carcinoma, an interim report. J. Clin. Oncol. 12, 1572 (1994).

    PubMed  CAS  Google Scholar 

  65. P. Lissoni, S. Barni, A. Ardizzoia et al.: Prognostic factors of the clinical response to subcutaneous immunotherapy with interleukin-2 alone in patients with metastatic renal cell carcinoma. Oncology 51, 59 (1994).

    Article  PubMed  CAS  Google Scholar 

  66. L.T. Vlasveld, S. Horenblas, A. Hekman et al.: Phase II study of intermittent continuous infusion of low-dose recombinant interleukin-2 in advanced melanoma and renal cell cancer. Ann. Oncol. 5, 179 (1994).

    PubMed  CAS  Google Scholar 

  67. R.P. Whitehead, D. Ward, L. Hemingway et al.: Subcutaneous recombinant inter-leukin-2 in a dose escalating regimen in patients with metastatic renal cell adenocarcinoma. Cancer Res. 50, 6708 (1990).

    PubMed  CAS  Google Scholar 

  68. D.T. Sleifer, R.A. Janssen, J. Buter et al.: Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. J. Clin. Oncol. 10, 1119 (1992).

    Google Scholar 

  69. S. Sone and T. Ogura: Local interleukin-2 therapy for cancer, and its effector induction mechanisms. Oncology 57, 170 (1994).

    Article  Google Scholar 

  70. P.M. Anderson and M.A. Sorenson: Effects of route and formulation on clinical pharmacokinetics of interleukin-2. Clin. Pharmacokinet. 27, 19 (1994).

    Article  PubMed  CAS  Google Scholar 

  71. P.M. Anderson, E. Katsanis, S.F. Sencer et al.: Depot characteristics and biodistribution of interleukin-2 liposomes: importance of route of administration. J. Immunother. 12, 19 (1992).

    Article  PubMed  CAS  Google Scholar 

  72. F.J. Meyers, C.Paradise, S.A.Scudder et al.: A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2. Clinical Pharmacol, and Therap. 49, 307(1991).

    Article  CAS  Google Scholar 

  73. L.P. Courtney, J.L. Phelps and L.M. Karavodin: An anti-IL-2 antibody increases serum halflife and improves anti-tumor efficacy of human recombinant interleukin-2. Immunopharmacology. 28, 223 (1994).

    Article  PubMed  CAS  Google Scholar 

  74. R.P. Whitehead, K.D. Friedman and D.A. Clark: A phase I trial of subcutaneous inter-leukin-2 and interleukin-4. Proc. Ann. Meet. Am. Assoc. Cancer Res. 33, A1381 (1992).

    Google Scholar 

  75. Y.C. Yang, L. Owen-Schaub, A. Mendiguren-Rodriquez et al.: Combination immunotherapy for non-small cell lung cancer-results with interleukin-2 and TNFa. J. Thorac. Cardiovasc. Surg. 79, 8 (1990).

    Google Scholar 

  76. U. Keilholz, C. Scheibenbogen, P. Brossart et al.: Interleukin-2-based immunotherapy and chemoimmunotherapy in metastatic melanoma. Recent Results Cane. Res. 139, 383 (1995).

    CAS  Google Scholar 

  77. M.S. Mitchell: Combining chemotherapy with biological response modifiers in the treatment of cancer. J. Natl. Cancer Inst. 80, 1445 (1988).

    Article  PubMed  CAS  Google Scholar 

  78. A.C. Buzaid and S.S. Legha: Combination of chemotherapy with interleukin-2 and interferon-alpha for the treatment of advanced melanoma. Seminars in Oncol. 21, 23 (1994).

    CAS  Google Scholar 

  79. D.M. Pardoll: Paracrine cytokine adjuvants in cancer immunotherapy. Annu. Rev. Immunol. 13, 399 (1995).

    Article  PubMed  CAS  Google Scholar 

  80. J. Triesman, P. Hwu, S. Minamoto, G.E. Shafer et al.: Interleukin-2-transduced lymphocytes grow in an autocrine fashion and remain responsive to antigen. Blood 85, 139 (1995).

    Google Scholar 

  81. P.A. Cassileth, E. Podack, K. Sridhar et al.: Clinical protocol: Phase I study of transfected cancer cells expressing the interleukin-2 gene product in limited stage small cell lung cancer. Human Gene Ther. 6, 369 (1995).

    Article  CAS  Google Scholar 

  82. B. Gansbacher: A pilot study of immunization with IL-2 secreting allogeneic HLA-A2 matched renal cell carcinoma cells in patients with advanced renal cell carcinoma. Human Gene Therapy 3, 691 (1992).

    Article  Google Scholar 

  83. Clinical Protocols. Cancer Gene Ther. 1, 289 (1994).

    Google Scholar 

  84. W. Schmidt, T. Schweighoffer, E. Herbst et al.: Cancer vaccines:The IL-2 dosage effect. Proc. Natl. Acad. Sci. USA 92, 4711 (1995).

    Article  PubMed  CAS  Google Scholar 

  85. J.A. Kovacs, M. Basier, R.J. Dewar et al.: Increases in CD4T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. N. Engl. J. Med. 332, 567 (1995).

    Article  PubMed  CAS  Google Scholar 

  86. Z.P Bernstein, M.M.Porter, M.Gould et al.: Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity. Blood 86, 3287 (1995).

    PubMed  CAS  Google Scholar 

  87. R.G. Hewitt: Interleukin-2; Full circle in a decade. Infect, in Med. July 490 (1994).

    Google Scholar 

  88. J.R. Minor: Interleukin-2 in HIV. Am. J. Health-Syst. Pharm. 52, 1345 (1995).

    PubMed  CAS  Google Scholar 

  89. M. Howard, J. Farrar, M. Hilfiker et al.: Identification of a T cell derived B-cell growth factor distinct from IL-2. J. Exp. Med. 155, 914 (1982).

    Article  PubMed  CAS  Google Scholar 

  90. T Yokota, T. Otsuka, T. Mosmann et al. Proc. Natl. Acad. Sci. USA 83, 5894 (1986).

    Article  CAS  Google Scholar 

  91. J. Banchereau, T. Defrance, J.P. Galizzi et al.: Human interleukin 4: Its agonistic and antagonistic effects on B lymphocytes and its receptor. In Cytokines: Basic Principles and Clinical Applications. S. Romagnani, A.K. Abbas (eds). Raven Press: New York 1990.177–187.

    Google Scholar 

  92. M.T. Lotze: Role of IL-4 in the antitumor response. In IL-4 Structure and Function. H. Spits (ed). CRC Press: Boca Raton, 19XX.

    Google Scholar 

  93. F.M. Hofman, M. Brock, CR. Taylor et al.: IL-4 regulates differentiation and proliferation of human precursor B cells. J. Immunol. 747, 1185 (1988).

    Google Scholar 

  94. J. Gordon, M.J. Mulsum, G.R. Guy et al.: Resting B lymphocytes can be triggered directly through the CDW40(Gp50) antigen. J. Immunol. 140, 1425 (1988).

    PubMed  CAS  Google Scholar 

  95. R. Noelle, PH. Karmmer, J. Ohara et al.: Increased expression of Ia antigen on resting B cells: a new role for B cell growth factor. Proc. Natl. Acad. Sci. USA 81, 6149 (1984).

    Article  PubMed  CAS  Google Scholar 

  96. CM. Snapper, F.D. Finkelman, W.E. Paul: Differential regulation of IgGl and IgE synthesis by interleukin 4. J. Exp. Med. 167, 183 (1988).

    Article  PubMed  CAS  Google Scholar 

  97. X. Han, K. Hoh, CM. Balch et al.: Recombinant interleukin 4 [RIL-4] inhibits interleukin-2 induced activation of peripheral blood lymphocytes. Lympho. Res. 7, 227 (1988).

    CAS  Google Scholar 

  98. H. Spits, H. Yssel, X. Paliard et al.: Interleukin 4 inhibits interleukin 2 mediated induction of human lymphokine activated killer cells, but not the generation of antigen specific cytotoxic T lymphocytes in mixed leukocyte cultures. J. Immunol. 141, 29 (1988).

    PubMed  CAS  Google Scholar 

  99. S.R. Carding, E.J. Jenkinson, R. Kingston et al.: Developmental control of lymphokine gene expression in fetal thymocytes during T cell ontogeny. Proc. Natl. Acad. Sci. USA 86, 2242 (1989).

    Article  Google Scholar 

  100. J. Ransom, M. Fischer, T. Mosmann et al.: Interferon gamma is produced by activated immature mouse thymocytes and reverses the interleukin 4-induced proliferation of immature thymocytes. J. Immunol. 139, 4102 (1987).

    PubMed  CAS  Google Scholar 

  101. M.D. Mossalayi, J.C. Lecron, A.H. Dalloul, et al Soluble CD23 (FcE) and interleukin 1 synergistically induce early human thymocyte maturation. J. Exp. Med. 171, 959 (1990).

    Article  PubMed  CAS  Google Scholar 

  102. J. Hu-Li, E.M. Sherach, J. Mizuguchi et al.: B cell stimulatory factor I (interleukin 4) is a potent costimulant for normal resting T lymphocytes. J. Exp. Med. 765, 157 (1987).

    Article  Google Scholar 

  103. H. Luo, M. Rubio, G. Biron et al.: Anti-proliferative effect of IL-4 in B chronic lymphocytic leukemia. J. Immunol, in press (ref from Spits).

    Google Scholar 

  104. M. Bosco, M. Giovarelli, M. Forni et al.: Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently non-immunogenic tumors and induce a tumor-specific immune memory. J. Immunol. 145, 3136 (1990).

    PubMed  CAS  Google Scholar 

  105. R.I. Tepper, P.K. Pattengale and P. Leder: Murine interleukin 4 displays potent anti-tumor activity in vivo. Cell 57, 503 (1989).

    Article  PubMed  CAS  Google Scholar 

  106. E.R. Fearon, D.M. Pardoll, T. Itanya et al.: Interleukin 2 production by tumor cells bypasses T helper function in the generation of an anti-tumor response. Cell 60, 397 (1990).

    Article  PubMed  CAS  Google Scholar 

  107. B. Gansbacher, R. Bannerji, B. Daniels et al.: Retroviral vector-mediated gamma interferon gene transfer into tumor cells generates potent and long lasting anti-tumor immunity. Cancer Res. 50, 7820 (1990).

    PubMed  CAS  Google Scholar 

  108. Y. Kawakami, S.A. Rosenberg and M.T. Lotze: Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes for human autologous melanoma. J. Exp. Med. 168, 2183 (1988).

    Article  PubMed  CAS  Google Scholar 

  109. M.H. Gilleece, J.H. Scarffe, A. Ghosh et al.: Recombinant human interleukin 4 (IL-4) given as daily subcutaneous injections - a phase I dose toxicity trial. Brit. J. Cancer 66, 204 (1992).

    Article  PubMed  CAS  Google Scholar 

  110. C.W. Taylor, TM. Grogan and S.E. Salmon: Effects of interleukin 4 on the in vitro growth of human lymphoid and plasma cell neoplasms. Blood 75, 1114 (1990).

    PubMed  CAS  Google Scholar 

  111. F. Herrman, M. Andreeff, H.J. Gruss et al.: Interleukin-4 inhibits growth of multiple myelomas by suppressing interleukin 6 expression. Blood 78, 2070 (1991).

    Google Scholar 

  112. T. Defrance, A.C. Fluckiger, J.-F. Rossi et al.: Antiproliferative effects of interleukin 4 on freshly isolated non-Hodgkin malignant B-lymphoma cells. Blood 79, 990 (1992).

    PubMed  CAS  Google Scholar 

  113. TE. Tanner and G. Tosato: Regulation of B-cell growth and immunoglobulin gene transcription by interleukin-6. Blood 79, 452 (1992).

    PubMed  CAS  Google Scholar 

  114. J. Van Snick: Interleukin-6: An overview. Annu. Rev. Immunol. 8, 253 (1990).

    Article  PubMed  Google Scholar 

  115. T. Hirano, S. Akira, T. Tetsuya and T Kishimoto: Biological and clinical aspects of interleukin 6. Immunol. Today 77, 443 (1990).

    Google Scholar 

  116. K. Yamasaki, T Taga, Y. Hirata et al.: Cloning and expression of the human inter-leukin-6 [BSF-2/IFNb2] receptor. Science 241, 825 (1988).

    Article  PubMed  CAS  Google Scholar 

  117. T. Taga, M. Hibi, Y. Hirata et al.: Interleukin-6 triggers the association of its receptor with a possible signal transducer gpl30. Cell 58, 573 (1989).

    Article  PubMed  CAS  Google Scholar 

  118. T. Ishibashi, H. Kimura, Y. Shikama et al.: Interleukin-6 is a potent thrombopoietic factor in vivo in mice. Blood 74, 1241 (1989).

    PubMed  CAS  Google Scholar 

  119. J. Weber, J.C. Yang, S.L. Topalian et al.: Phase I trial of subcutaneous interleukin-6 in patients with advanced malignancies. J. Clin. Oncol. 11, 499 (1993).

    PubMed  CAS  Google Scholar 

  120. D. Caracciolo, S.C. Clark and G. Rovera: Human interleukin-6 supports granulocytic differentiation of hematopoietic progenitor cells and acts synergistically with GM-CSG. Blood 73, 666 (1989).

    PubMed  CAS  Google Scholar 

  121. T. Olencki, GT Budd, S. Murthy et al.: Phase IA/IB trial of rhIL-6 in patients with refractory malignancy: hematologic and immunologic effects. Blood Suppl 1, 89a (1992).

    Google Scholar 

  122. J.J. Mulé, J.K. Mcintosh, D.M. Jablons et al.: In vivo administration of recombinant interleukin-6 mediates tumor regression in mice. J. Exp. Med. 171, 629 (1990).

    Article  PubMed  Google Scholar 

  123. J.J. Mulé, S.G. Marcus, J.C. Yang et al.: Clinical applications of IL-6 in cancer therapy. Res. Immunol. 143, 777 (1992).

    Article  PubMed  Google Scholar 

  124. Porgator, E.Tzehoval, A. Katz et al.: IL-6 gene transfection into 3LL tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells. Cancer Res. 52, 3679 (1992).

    Google Scholar 

  125. Scheid, R. Young, R. McDermott et al.: Immune function of patients receiving recombinant human interleukin-6 (IL-6) in a phase I clinical study: induction of C-reactive protein and IgE and inhibition of natural killer and lymphokine-activated killer cell activity. Cancer Immunol. Immunother. 38, 119 (1994).

    PubMed  CAS  Google Scholar 

  126. J. Malejczyk, M. Malejczyk, A. Urbanski and T.A. Luger: Production of natural killer cell activity-augmenting factor (interleukin-6) by human epiphyseal chondrocytes. Arthritis Rheum. 35, 706 (1992).

    Article  PubMed  CAS  Google Scholar 

  127. H. Goto, C. Shimazaki, T Tatsumi et al.: Establishment of a novel myeloma cell line KPMM2 carrying t(3;14)(q21;q32), which proliferates specifically in response to inter-leukin-6 through an autocrine mechanism. Leukemia 9, 711 (1995).

    PubMed  CAS  Google Scholar 

  128. O.F. Ballester, L.C. Moscinski, G.H. Lyman et al.: High levels of interleukin-6 are associated with low tumor burden and low growth fraction in multiple myeloma. Blood 83, 1903 (1994).

    PubMed  CAS  Google Scholar 

  129. H.J. Gruss, M.A. Brach, R.H. Mertelsmann and F. Herrmann: Interferon-gamma interrupts autocrine growth mediated by endogenous interleukin-6 in renal-cell carcinoma. International J. Cancer 11, 770 (1991).

    Article  Google Scholar 

  130. M. Rabau, H. Kashtan, S. Baron et al.: Inhibition of CT-26 murine adenocarcinoma growth in the rectum of mice treated with recombinant human interleukin-6. J. Immu-nother. Emphasis Tumor. Immunol. 15, 257 (1994).

    CAS  Google Scholar 

  131. K.W. Moore, R Vieira, D.F. Fiorentino et al.: Homology of cytokine synthesis inhibitory factor (IL-10) to Epstein-Barr virus gene BCRF1. Science 248, 1230 (1990).

    Article  PubMed  CAS  Google Scholar 

  132. M.R. Walter and T.L. Nagabhushan: Crystal structure of interleukin-10 reveals an interferon gamma-like fold. Biochemistry 34, 12118 (1995).

    Article  PubMed  CAS  Google Scholar 

  133. A. Zdanov, C. Schalk-Hihi, A. Gustchina et al.: Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure 3, 591 (1995).

    Article  PubMed  CAS  Google Scholar 

  134. Y. Lui, S.H. Wei, A.S. Ho et al.: Expression cloning of the human IL-10 receptor. J. Immunol. 15, 1821 (1994).

    Google Scholar 

  135. K.W. Moore, A.O’Garra, M. de Waal et al.: Interleukin-10. Ann. Rev. Immunol. 77, 165 (1993).

    Article  Google Scholar 

  136. K.Taga and G.Tosato: IL-10 inhibitsT-cell proliferation and IL-2 production.J Immunol. 148, 1143 (1992).

    PubMed  CAS  Google Scholar 

  137. M. de Waal, R.J. Abrams, B. Bennet et al.: Interleukin-10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J. Exp. Med. 174, 1209 (1991).

    Article  Google Scholar 

  138. WE. Carson, M.J. Lindemann, R. Baiocchi et al.:The functional characterization of interleukin-10 receptor expression on human natural killer cells. Blood 85, 3577 (1995).

    PubMed  CAS  Google Scholar 

  139. A.E. Chernoff, E.V. Granowitz, L. Shapiro et al.: A randomized, controlled trial of IL-10 in humans. J. Immunol. 154, 5492 (1995).

    PubMed  CAS  Google Scholar 

  140. H. Tahara and M.T. Lotze: Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer. Gene Therapy 2, 96 (1995).

    PubMed  CAS  Google Scholar 

  141. G.Trinchieri and R Scott: The role of interleukin 12 in the immune response, disease and therapy. Immunol. Today 15, 460 (1994).

    CAS  Google Scholar 

  142. F.D. Finkelman: Relationships among antigen presentation, cytokines, immune deviation, and autoimmune disease. J. Exp. Med. 182, 279 (1995).

    Article  PubMed  CAS  Google Scholar 

  143. M.J. Skeen and H.K. Ziegler: Activation of y8 T cells for production of IFN-γ is mediated by bacteria via macrophage-derived cytokines IL-1 and IL-12. J. Immunol. 154, 5832 (1995).

    PubMed  CAS  Google Scholar 

  144. R.T. Gazzinelli, S. Hayashi, M. Wysocka et al.: Role of IL-12 in the initiation of cell mediated immunity by Toxoplasma gondii and its regulation by IL-10 and nitric oxide. J. Eukaryotic Microbiol. 41, 9S (1994).

    CAS  Google Scholar 

  145. M. Denis: Interleukin-12 (IL-12) augments cytolytic activity of natural killer cells toward Mycobacterium tuberculosis-infected human monocytes. Cellular Immunol. 156, 529 (1994).

    Article  CAS  Google Scholar 

  146. C.L. Nastala, H.D. Edington, T.G McKinney et al.: Recombinant IL-12 administration induces tumor regression in association with IFN-oc production. J. Immunol. 153, 1697 (1994).

    PubMed  CAS  Google Scholar 

  147. Kelso: Thl and Th2 subsets: paradigms lost. Immunol. Today 16, 374 (1995).

    CAS  Google Scholar 

  148. TA. Wynn, D. Jankovic, S. Hieny et al.: IL-12 exacerbates rather than suppresses T helper 2-dependent pathology in the absence of endogenous IFN-γ. J. Immunol. 154, 3999 (1995).

    PubMed  CAS  Google Scholar 

  149. D’Andrea, X. Ma, M. Aste-Amezaga et al.: Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: Priming for IL-12 and tumor necrosis factor a production. J. Exp. Med. 181, 537 (1995).

    Article  PubMed  Google Scholar 

  150. T.A. Wynn, D. Kankovic, S. Hieny et al.: IL-12 enhances vaccine-induced immunity to Schisotoma mansoni in mice and decreases T helper 2 cytokine expression, IgE production, and tissue eosinophilia. J. Immunol. 154, 4701 (1995).

    PubMed  CAS  Google Scholar 

  151. S.S. Hall: IL-12 at the crossroads. Science 268, 1432 (1995).

    Article  PubMed  CAS  Google Scholar 

  152. CM. Bacon, D.W. McVicar, J.R. Ortaldo et al.: Interleukin-12 (IL-12) induces tyrosine phosphorylation of JAK2 and TYK2: differntial use of Janus family tyrosine kinases by 11–2 and IL-12. J. Exp. Med. 181, 399 (1995).

    Article  PubMed  CAS  Google Scholar 

  153. K.H. Grabstein, J. Eisenman, K. Shanebeck et al.: Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264, 965 (1994).

    Article  PubMed  CAS  Google Scholar 

  154. J.G. Giri, M. Ahdieh, J. Eisenmann et al.: Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J. 13, 2822 (1994).

    PubMed  CAS  Google Scholar 

  155. J. Giri, S. Kumaki, M. Ahdieh et al.: Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor. EMBO J. 14, 3654 (1995).

    PubMed  CAS  Google Scholar 

  156. R.J. Armitage, B.M. Macduff, J. Eisenman et al.: IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation. J. Immunol. 15, 483 (1995).

    Google Scholar 

  157. WM. Lewko, T.L. Smith, D.J. Bowman et al.: Interleukin-15 and the growth of tumor derived activated T-cells. Cancer Biother. 10, 13 (1995).

    Article  PubMed  CAS  Google Scholar 

  158. W. Munger, S.Q. DeJoy, R. Jeyaseelan Sr. et al.: Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: Comparison with interleukin-2. Cellular Immunol. 165, 289 (1995).

    Article  CAS  Google Scholar 

  159. L.S. Quinn, K.L. Haugk and K.H. Grabstein: Interleukin-15: A novel anabolic cytokine for skeletal muscle. Endocrinology 126, 3669 (1995).

    Article  Google Scholar 

  160. E.C Borden: Interferons. In: Cancer Medicine. J.F. Holland et al. (eds). 1993. Lea & Feabiger: Philadelphia.

    Google Scholar 

  161. S.E. Grossberg: Interferons: an overview of their biological and biochemical properties. In Mechanism of Interferon Actions. L.M. Pfeffer (ed). 1987. CRC Press, Ine: Boca Raton, p. 137.

    Google Scholar 

  162. A.A. Branca and C. Baglioni: Evidence that types I and II interferons have different receptors. Nature 294, 768 (1981).

    Article  PubMed  CAS  Google Scholar 

  163. M. Aguet, Z. Dembic and G. Merlin: Molecular cloning and expression of the human interferon-g receptor. Cell 55, 273 (1988).

    Article  PubMed  CAS  Google Scholar 

  164. R.D. Schreiber and M.A. Farrar: The biology and biochemistry of interferon-gamma and its receptor. Gastroenterol. Jpn. 4, 88 (1993).

    Google Scholar 

  165. J.L. Pace and S.W. Russell: Activation of mouse macrophages for tumor cell killing. Quantitave analysis of interactions between lymphokine and lipopolysaccharide. J. Immunol. 726, 1863 (1981).

    Google Scholar 

  166. L. Reid, N. Minato, I. Gresser et al.: Influence of antimouse interferon serum on the growth and metastasis of tumor cells persistently infected by virus and of human prostatic tumors in athymic mice. Proc. Natl. Acad. Sci. 78, 1171 (1981).

    Article  PubMed  CAS  Google Scholar 

  167. Gresser, F. Belardelli, C. Maury et al.: Injection of mice with antibody to interferon enhances the growth of murine transplantable tumors. J. Exp. Med. 158, 2095 (1983).

    Article  PubMed  CAS  Google Scholar 

  168. A.E. Maluish: Effects of recombinant interferon-alpha on immune function in cancer patients. J. Biol. Response Mod. 2,470 (1983).

    PubMed  CAS  Google Scholar 

  169. M. Fellous, U. Nir, D. Wallach et al.: Interferon-dependent induction of mRNA for the major histocompatability antigens in human fibroblasts and lymphoblastoid cell lines. Proc. Natl. Acad. Sci. 79,3082,1982.

    Article  PubMed  CAS  Google Scholar 

  170. R.C. van Schie, H.G. Verstraten, W.J.Tax et al.: Effect of rIFN-gamma on antibody-mediated cytotoxicity via human monocyte IgG Fc receptor II (CD32). Scand. J. Immunol. 36, 385 (1992).

    Article  PubMed  Google Scholar 

  171. A.A. te Velde, R. de Waal Malefijt, R.J. Huijbens et al.: IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL-4, and IL-10. J. Immunol. 149, 4048 (1992).

    Google Scholar 

  172. WM. Vuist, M.J. Visseren, M. Otsen et al.: Enhancement of the antibody-dependent cellular cytotoxicity of human peripheral blood lymphocytes with interleukin-2 and interferon alpha. Cancer Immunol. Immunother. 36, 163 (1993).

    Article  PubMed  CAS  Google Scholar 

  173. V. Jendrossek, A.M. Peters, S. Buth et al.: Improvement of superoxide production in monocytes from patients with chronic granulomatous disease by recombinant cytokines. Blood 81, 2131 (1993).

    PubMed  CAS  Google Scholar 

  174. M.J. Robertson, T.J. Manley, C. Donahue et al.: Costimulatory signals are required for optimal proliferation of human natural killer cells. J. Immunol. 150, 1705 (1993).

    PubMed  CAS  Google Scholar 

  175. M.J. Robertson and J. Ritz: Biology and clinical relevance of human natural killer cells. Blood 76,2421 (1990).

    PubMed  CAS  Google Scholar 

  176. J.R. Wunderlich and R.J. Hodes: Principles of Tumor Immunity: Biology of Cellular Immune Responses, in: Biologic Therapy of Cancer, V.T. Devita, S. Hellman, S.A. Rosenberg (eds). 1991. J. B. Lippincott: New York. p. 14.

    Google Scholar 

  177. N. Minato, L. Reid, H. Cantor et al.: Mode regulation of natural killer cell activity by intereferon. J. Exp. Med. 152, 124 (1980).

    Article  PubMed  CAS  Google Scholar 

  178. C. Losinno, B.D. Wines, T.G. Johns et al.: Natural killer cell activity against cultured melanoma cells: a dye-reduction technique with studies on augmented activity by interferon subtypes. Nat. Immun. 11, 215 (1992).

    PubMed  CAS  Google Scholar 

  179. M.A. Giedlund, H. Orn and H. Wigzell: Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 273, 759 (1987).

    Article  Google Scholar 

  180. E. Saksela, T. Timonen and K. Cantell: Cellular Interactions in the augmentation of human NK activity by interferon. Ann. NY Acad. Sci. 350, 102 (1980).

    Article  PubMed  CAS  Google Scholar 

  181. R.M. Welsh, K. Karre, M. Hansson et al: Interferon-mediated protection of normal and tumor target cells against lysis by mouse natural killer cells. J. Immunol. 1, 219 (1981).

    Google Scholar 

  182. C. Garbe and K. Krasagakis: Effects of interferons and cytokines on melanoma cells. J. Invest. Derm. 100, 239S (1993).

    Article  PubMed  CAS  Google Scholar 

  183. H. Matsuyama, S. Yoshihiro, Y. Ohmoto et al.: Direct and indirect effects of human interferon alpha on renal cell carcinoma: a new in vitro assay system for evaluating cytokine-mediated antitumor effects. Cancer Immunol. Immunother. 37, 84 (1993).

    Article  PubMed  CAS  Google Scholar 

  184. Z. Reiter, S. Tomson, O.N. Ozes et al.: Combination treatment of 2-chlorodeoxya-denosine and type I interferon on hairy cell leukemia-like cells: cytotoxic effect and MHC-unrestricted killer cell regulation. Blood 81,1699 (1993).

    PubMed  CAS  Google Scholar 

  185. E.F. Meurs, J. Galabru, G.N. Barber et al.: Tumor suppressor function of the inter-feron-induced double-stranded RNA-activated protein kinase. Proc. Natl. Acad. Sci. 90, 232 (1993).

    Article  PubMed  CAS  Google Scholar 

  186. R. Godbout, J. Miyakoshi, K.D. Dobler et al.: Lack of expression of tumor-suppressor genes in human malignant glioma cell lines. Oncogene 7, 1879 (1992).

    PubMed  CAS  Google Scholar 

  187. O.I. Olopade, D.L. Buchhagen, K. Malik et al.: Homozygous loss of the interferon genes defines the critical region on 9p that is deleted in lung cancers. Cancer Res. 53 (Suppl. 10), 2410 (1993).

    PubMed  CAS  Google Scholar 

  188. C. Natoli, C. Garufi, N.Tinari et al.: Dynamic test with recombinant interferon-alpha-2b: effect on 90K and other tumour-associated antigens in cancer patients without evidence of disease. Br. J. Cancer 67, 564 (1993).

    Article  PubMed  CAS  Google Scholar 

  189. R.L. Scher, W.M. Koch and W.J. Richtsmeier: Induction of the intercellular adhesion molecule (ICAM-1) on squamous cell carcinoma by interferon gamma. Arch. Otolaryngol. Head Neck Surg. 119, 432 (1993).

    PubMed  CAS  Google Scholar 

  190. H. Takahashi, Y. Okai, R.J. Paxton et al.: Differential regulation of carcinoembryonic antigen and biliary glycoprotein by gamma-interferon. Cancer Res. 53, 1612 (1993).

    PubMed  CAS  Google Scholar 

  191. N. Weidner, J.P. Semple, W.R.Welch et al.: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N. Engl. J. Med. 324, 1 (1991).

    Article  PubMed  CAS  Google Scholar 

  192. N. Weidner, J. Folkman, F. Dozza et al.: Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma [see comments]. J. Natl. Cancer Inst. 84, 1875 (1992).

    Article  PubMed  CAS  Google Scholar 

  193. Saiki, K. Sato, Y.C. Yoo et al.: Inhibition of tumor-induced angiogenesis by the administration of recombinant interferon-gamma followed by a synthetic lipid-A subunit analogue (GLA-60). Intl. J. Cancer 51, 641 (1992).

    Article  CAS  Google Scholar 

  194. J. Folkman and D. Ingber: Inhibition of angiogenesis. Semin. Cancer Biol. 3, 89 (1992).

    CAS  Google Scholar 

  195. C. W. White: Treatment of hemangiomatosis with recombinant interferon alfa. Semin. Hematol. 27, 15 (1990).

    PubMed  CAS  Google Scholar 

  196. R.K. Maheshwari, V. Srikantan, D. Bhartiya et al.: Differential effects of interferon gamma and alpha on in vitro model of angiogenesis. J. Cell. Physiol. 146,164 (1991).

    Article  PubMed  CAS  Google Scholar 

  197. D.C. Billington: Angiogenesis and its inhibition: potential new therapies in oncology and non-neoplastic diseases. Drug Des. Discov. 8, 3 (1991).

    PubMed  CAS  Google Scholar 

  198. J.R. Quesada, J. Reuben, J.T. Manning et al.: Alpha interferon for the induction of remission in hairy-cell leukemia. N. Engl. J. Med. 310, 15 (1984).

    Article  PubMed  CAS  Google Scholar 

  199. R. Dadmarz, T. Evans, D. Secher et al.: Hairy cells possess more interferon receptors than other lymphoid cell types. Leukemia 1, 357 (1987).

    PubMed  CAS  Google Scholar 

  200. J.D. Scharzmeier, M. Schwabe, L. Wagner et al.: Effect of alpha-2-interferon on hairy cells and cell lines. A role for type I interferon receptors and RNA synthesis. Leu-kemia 1, 361 (1987).

    Google Scholar 

  201. M. Talpaz, H.M. Kantarjain, K.B. McCerdie et al.: Clinical investigation of human alpha interferon in chronic myelogenous leukemia. Blood 69, 1280, (1987).

    PubMed  CAS  Google Scholar 

  202. R. Kurzrock, M. Talpaz, H.M. Kantarjain et al.: Therapy of chronic myelogenous leukemia with recombinant interferon-gamma. Blood 70, 943 (1987).

    PubMed  CAS  Google Scholar 

  203. B. Maxwell, M. Talpaz and J.U. Gutterman: Down regulation of peripheral blood cell interferon receptors in chronic myelogenous leukemia patients undergoing human interferon (HuIFN) therapy. Intl. J. Cancer. 36, 23 (1985).

    Article  CAS  Google Scholar 

  204. M. Rosenblum, B. Maxwell, M. Talpaz et al.: In vitro sensitivity and resistance of chronic myelogenous leukemia cells to alpha interferon: Correlation with receptor binding and induction of 2’5’oligoadenylate synthetase. Cancer Res. 46, 4848 (1986).

    PubMed  CAS  Google Scholar 

  205. E. Knight, Jr., E.D. Anton, D. Fahey et al.: Interferon regulates c-myc gene expression in Daudi cells at the post-transcriptional level. Proc. Natl. Acad. Sci. USA 82, 1151 (1985).

    Article  PubMed  CAS  Google Scholar 

  206. J.R. Quesada, D.A. Swanson, A. Trindade et al.: Renal Celi Carcinoma: Antitumor effects of leukocyte interferon. Cancer Res. 43, 940 (1983).

    PubMed  CAS  Google Scholar 

  207. J.M. Kirkwood, IE. Harris, R. Vera 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. 45, 863 (1985).

    PubMed  CAS  Google Scholar 

  208. T. Umeda and T. Niijima: Phase II study of alpha interferon on renal cell carcinoma. Cancer 58, 1231 (1986).

    Article  PubMed  CAS  Google Scholar 

  209. H.B. Muss, J.J. Costanzi, R. Leavitt et al.: Recombinant alfa interferon in renal cell carcinoma: A randomised trial of two routes of administration. J. Clin. Oncol. 5, 286 (1987).

    PubMed  CAS  Google Scholar 

  210. Figlin, R.A., J.B. deKernion, E. Mukamel et al.: Recombinant interferon alfa-2a in metastatic renal cell carcinoma. J. Clin. Oncol. 6, 1604 (1988).

    PubMed  CAS  Google Scholar 

  211. D. Vugrin, L. Hood, W. Taylor and J. Laslo: Phase II study of human lymphoblastoid Interferon in patients with advanced renal carcinoma. Cancer Treat. Reports 69, 817 (1985).

    CAS  Google Scholar 

  212. E.T. Creagan, J.C. Buckner, R.G. Hahn et al.: An evaluation of recombinant leucocyte interferon with aspirin in patients with metastatic renal cell cancer. Cancer 61, 1787 (1988).

    Article  PubMed  CAS  Google Scholar 

  213. R.L. Miller, R.G. Stess, J.W. Clark et al.: Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Res. 49, 1871 (1989).

    PubMed  CAS  Google Scholar 

  214. S.D. Fossâ, G. Lehne, R. Gunderson et al.: Recombinant interferon alpha-2A combined with prednisone in metastatic renal-cell carcinoma: treatment results, serum interferon levels and the development of antibodies. Intl. J. Cancer 50, 868 (1992).

    Article  Google Scholar 

  215. T.F. Logan, M.S. Ernstoff, J.M. Kirkwood, B. Gerich, D. Friberg, T.Whiteside, B. Eddy, P. Witman, J. Schindler, R.B. Herberman and S. Reich: Changes in natural killer cell (NK) phenotype in peripheral blood (PB) of patients (PT) with renal cell carcinoma and melanoma treated with recombinant interferon gamma (IFN-gamma). Proc. Am. Assoc. Cancer Res. 78, 2520A (1987).

    Google Scholar 

  216. M.B. Garnick, S.D. Reich and B.E. A. Maxwell: Phase I/II study of recombinant interferon gamma in advanced renal cell carcinoma. J. Urol. 139, 251 (1988).

    PubMed  CAS  Google Scholar 

  217. J.R. Quesada, R. Kurzrock, S.A. Sherwin et al.: Phase II studies of recombinant human interferon gamma in metastatic renal cell carcinoma. J. Biol. Response Mod. 6, 20 (1987).

    PubMed  CAS  Google Scholar 

  218. J.J. Rinehart, L. Malspeis, D. Young et al.: Phase I/II Trial of human recombinant interferon gamma in renal cell carcinoma. J. Biol. Response Mod. 5, 300 (1986).

    PubMed  CAS  Google Scholar 

  219. U. Otto, S. Conrad, A.W Schneider et al.: Recombinant interferon gamma in the treatment of metastatic renal cell carcinoma. Drug Res. 38, 1658 (1988).

    CAS  Google Scholar 

  220. W. Aulitzky, G. Gastl, WE. Aulitzky et al.: Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma. J. Clin. Oncol. 7, 1875 (1989).

    PubMed  CAS  Google Scholar 

  221. U. Bruntsch, PH. de Mulder, WW ten Bokkel Huinink et al.: Phase II study of recom-binant human interferon-gamma in metastatic renal cell carcinoma. J. Biol. Response Mod. 9, 335 (1990).

    PubMed  CAS  Google Scholar 

  222. C.W. Czarniecki, C.W Fennie, D.B. Powers et al.: Synergistic antiviral and antipro-liferative activities of E coli derived human alpha, beta and gamma interferons. J. Virol. 49, 490 (1984).

    PubMed  CAS  Google Scholar 

  223. K. Foon, J. Doroshow, E. Bonnern et al.: A prospective randomized trial of alpha2b interferon/gamma interferon or the combination in advanced metastatic renal cell carcinoma. J. Biol. Response Mod. 7, 540 (1988).

    PubMed  CAS  Google Scholar 

  224. J.R. Quesada, L. Evans, S.R. Saks et al.: Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma. J. Biol. Response Mod. 7, 234 (1988).

    PubMed  CAS  Google Scholar 

  225. M.S. Ernstoff, S. Nair, R.R. Bahnson et al.: A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 8,1637 (1990).

    PubMed  CAS  Google Scholar 

  226. M.S. Ernstoff, W. Gooding, S. Nair et al.: Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial. Cancer Res. 52, 851 (1992).

    PubMed  CAS  Google Scholar 

  227. J.R Kuebler, G.A. Godette, D.J. Bock et al.: Synergistic effects of vinblastine and recombinant interferon-beta on renal tumor cell lines. J. Interferon Res. 10, 281 (1990).

    Article  PubMed  CAS  Google Scholar 

  228. R.A. Figlin, J.B. deKernion, J. Maldazys et al.: Treatment of renal cell carcinoma with alpha(human leukocyte) interferon and vinblastine in combination: A phase I-II trial. Cancer Treat. Reports 69, 263 (1985).

    CAS  Google Scholar 

  229. S.D. Fossâ and S.T. de Garis: Further experience with recombinant interferon alfa-2a with vinblastine in metastatic renal cell carcinoma: a progress report. Intl. J. Can-cer Suppl 1, 36 (1987).

    Article  Google Scholar 

  230. M.R. Sertoli, I. Brunetti, A. Ardizzoni et al.: Recombinant alpha-2a interferon plus vinblastine in the treatment of metastatic renal cell carcinoma. Am. J. Clin. Oncol. 12, 43 (1989).

    Article  PubMed  CAS  Google Scholar 

  231. S.D. Fossâ, N. Raabe and B. Moe: Recombinant interferon-alpha with or without vinblastine in metastatic renal carcinoma. Results of a randomised phase II study. Br. J. Urol.64, 468 (1989).

    Article  PubMed  Google Scholar 

  232. S. Palmeri, V. Gebbia, A. Russo et al.: Vinblastine and interferon-alpha-2a regimen in the treatment of metastatic renal cell carcinoma. Tumori 76, 64 (1990).

    PubMed  CAS  Google Scholar 

  233. D.L. Trump, RM. Ravdin, E.C Borden et al.: Interferon-alpha-nl and continuous infusion vinblastine for treatment of advanced renal cell carcinoma. J. Biol. Res-ponse Mod. 9, 108 (1990).

    CAS  Google Scholar 

  234. L.P Kellokumpu and E. Nordman: Recombinant interferon-alpha 2a and vinblastine in advanced renal cell cancer: a clinical phase I-II study. J. Biol. Response Mod. 9, 439 (1990).

    Google Scholar 

  235. M. Rizzo, R. Bartoletti, C. Selli et al.: Interferon alpha-2a and vinblastine in the treatment of metastatic renal carcinoma. Eur. Urol. 16, 271 (1989).

    PubMed  CAS  Google Scholar 

  236. O. Merimsky and S. Chaitchik: Interferon plus vinblastine in renal carcinoma patients who had failed on interferon alone [letter]. Eur. J. Cancer 26, 8 (1990).

    Google Scholar 

  237. O. Merimsky, B.I. Shnider and S. Chaitchik: Does vinblastine add to the potency of alpha interferon in the treatment of renal cell carcinoma? Mol. Biother. 3, 34 (1991).

    PubMed  CAS  Google Scholar 

  238. Sella, C.J. Logothers, K. Fitz et al.: Phase II study of interferon-alpha and che-motherapy (5-fluorouracil and mitomycin C) in metastatic renal cell cancer. J. Urol. 147, 573 (1992).

    PubMed  CAS  Google Scholar 

  239. H.J. Konig, W. Gutmann and J. Weissmuller: Ifosfamide, vindesine and recombinant alpha-interferon combination chemotherapy for metastatic renal cell carcinoma. J. Cancer Res. Clin. Oncol. 117, S221 (1991).

    Article  PubMed  Google Scholar 

  240. Falcone, C. Cianci, S. Ricci et al.: Alpha-2B-interferon plus floxuridine in meta¬tatic renal cell carcinoma. A phase I-II study. Cancer Diag. Treat. Res. 72, 564 (1993).

    CAS  Google Scholar 

  241. H.B. Muss: Renal Cell Carcinoma. In: Biologie Therapy of Cancer, V.T. Devita, S. Hellman, S.A. Rosenberg (eds). 1991. J.B. Lippincott: New York. p. 298–309.

    Google Scholar 

  242. L.M. Minasian, R.J. Motzer, L. Gluck 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. 11, 1368 (1993).

    PubMed  CAS  Google Scholar 

  243. S.E. Salmon, B.G. Durie, L. Young et al.: Effects of cloned human leukocyte interferons in the human tumor stem cell assay. J. Clin. Oncol. 1, 217 (1983).

    PubMed  CAS  Google Scholar 

  244. P.P. Trotta and S.D. Harrison, Jr.: Evaluation of the anti-tumor activity recombinant human gamma interferon employing human melanoma xenografts in athymic nude mice. Cancer Res. 47, 5347 (1987).

    PubMed  CAS  Google Scholar 

  245. M.S. Ernstoff, D. Chee, G. Witman et al.:The expression of p97, kd250, DR and beta-2 microglobulin cell surface antigen in cycling melanoma cells in culture (Abstract). Clin. Res. 32, 345A (1984).

    Google Scholar 

  246. J.M. Kirkwood and M.S. Ernstoff: Melanoma: therapeutic options with recombinant interferons Semin. Oncol. 12, 7 (1985).

    CAS  Google Scholar 

  247. J.M. Kirkwood, M.H. Stawderman, M.S. Ernstoff et al.: Interferon alpha-2b adjuvant therapy of high risk resected cutaneous melanoma: The Eastern Cooperative Oncology Group Trial EST1684. J. Clin. Oncol. 14, 7 (1996).

    PubMed  CAS  Google Scholar 

  248. B. Beutler, D. Greenwald, J.D. Hulmes et al: Identity of tumour necrosis factor and the macrophage-secreted factor ’cachectin’. Nature 316, 552 (1985).

    Article  PubMed  CAS  Google Scholar 

  249. K.J. Tracey and A. Cerami: Tumor necrosis factor: an updated review of its biology. Crit. Care Med. 21 (10 Suppl), S415 (1993).

    CAS  Google Scholar 

  250. A.S. Dofferhoff, E. Vellenga, RC. Limburg et al.: Tumour necrosis factor (cachectin) and other cytokines in septic shock: a review of the literature. Nether. J. Med. 39,45 (1991).

    CAS  Google Scholar 

  251. K.J. Tracey and A. Cerami: Metabolic responses to cachectin/TNF. A brief review. Ann. NY. Acad. Sci. 587,325 (1990).

    CAS  Google Scholar 

  252. P. Vassalli: The pathophysiology of tumor necrosis factor. Ann. Rev. Immunol. 10, 411 (1992).

    Article  CAS  Google Scholar 

  253. B.B. Aggarwal and J. Vilcek (eds.): Tumor Necrosis Factor: Structure, Function and Mechanisms of Action. 1992. New York: Marcel Dekker.

    Google Scholar 

  254. E. Ottaviani, E. Caselgrandi and C. Franceschi: Cytokines and evolution: in vitro effects of IL-1 alpha, IL-1 beta, TNF-alpha and TNF-beta on an ancestral type of stress response. Biochem. Biophys. Res. Commun. 207,288 (1995).

    Article  PubMed  CAS  Google Scholar 

  255. D. Adamthwaite and M.A. Cooley: CD8+ T-cell subsets defined by expression of CD45 isoforms differ in their capacity to produce IL-2, IFN-gamma and TNF-beta. Immunol. 81,253 (1994).

    CAS  Google Scholar 

  256. C. Jassoy, T. Harr er, T. Rosenthal et al.: Human immunodeficiency virus type 1 -specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens. J. Virol. 67, 2844 (1993).

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Instituto Nationale per la Ricerca sul Cancro, Genova, Italy

    Gaetano Cardi

  2. Dartmouth Medical School, 03755, Hanover, NH, USA

    Thomas L. Ciardelli

  3. Research Service, Vetarans Administrations Hospital, White River Junction, 05009, VT, USA

    Thomas L. Ciardelli

  4. Dartmouth Medical School and Norris Cotton Cancer Center, Hanover, 03755, NH, USA

    Marc S. Ernstoff

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  1. Gaetano Cardi
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  2. Thomas L. Ciardelli
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  3. Marc S. Ernstoff
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  1. Steinweg 28, CH-4107, Ettingen, Switzerland

    Ernst Jucker

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© 1996 Birkhäuser Verlag, Basel (Switzerland)

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Cardi, G., Ciardelli, T.L., Ernstoff, M.S. (1996). Therapeutic applications of cytokines for immunostimulation and immunosuppression: An update. In: Jucker, E. (eds) Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques. Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques, vol 47. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-8998-8_6

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  • DOI: https://doi.org/10.1007/978-3-0348-8998-8_6

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