Urological Research

, Volume 18, Issue 6, pp 357–372

Rationale for immunotherapy of renal cell carcinoma

  • R. Heicappell
  • R. Ackermann
Invited Review


Metastasis to distant organs is the principal cause of death from renal cell carcinoma (RCC). No commonly accepted therapy is available for disseminated RCC at present. Immunotherapy is a mode of therapy that either interferes with the immune system or makes use of drugs that have been derived from soluble mediators of the immune system. Several lines of evidence suggest that combinations of genetically engineered cytokines (e.g. interleukin-2 and interferon alpha) may be particularly active in the treatment of advanced RCC. There are two major rationales for considering immunotherapy for RCC: (1) there is currently no other therapy available, and (2) there is hardly any innovative approach besides immunotherapy. Still, immunotherapy is far from being a standard therapy for disseminated RCC.

Key words

Renal cell carcinoma Immunotherapy Cytokines 


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  1. 1.
    Abrams J, Rayner A, Wiernik A, Parkinson D (1989) High dose interleukin-2 without lymphokine activated killer cells. Inactive in advanced renal cell cancer. Proc Am Assoc Cancer Res 30:A1507Google Scholar
  2. 2.
    Adams D, Hamilton TA (1984) The cell biology of macrophage activation. Ann Rev Immunol 2:283Google Scholar
  3. 3.
    Atzpodien J, Körfer A, Franks CR, Poliwoda H, Kirchner H (1990) Home therapy with recombinant interleukin-2 and interferon-α2b in advanced human malignancies. Lancet I:1509Google Scholar
  4. 4.
    Bander NH (1989) Monclonal antibodies to renal cancer antigens. Semin Urol VII:264Google Scholar
  5. 5.
    Bar MH, Valona FH, Rayner AA, Louie A, Aronson FR (1990) A phase I–II trial of combined interleukin-2 and vinblastine for metastatic renal cell carcinoma. Proc Ann Meet Am Soc Clin Oncol 9:A568Google Scholar
  6. 6.
    Bartsch HH, Pfizenmaier K, Schroeder M, Nagel GA (1989) Intralesional application of recombinant human tumor necrosis factor alpha induces local tumor regression in patients with advanced malignancies. Eur J Cancer Clin Oncol 25:287Google Scholar
  7. 7.
    Bartsch HH, Adler M, Ringert RH, Boaziz C, Symanns M, Humblet Y, Bosly A, Franks CR (1990) Sequential therapy of recombinant interferon-alpha (IFN-A) and recombinant interleukin 2(IL-2) in patients with advanced renal cell cancer (RCC). Proc Ann Meet Am Soc Clin Oncol 9:A556Google Scholar
  8. 8.
    Bassil B, Dosoretz DE, Prout GR Jr (1985) Validation of the tumor nodes and metastasis classification of renal cell carcinoma. J Urol 134:450Google Scholar
  9. 9.
    Bauer HW, Sudhoff F, Otto U, Wander HE, Schneider G, Jager N, Drees N (1984) Renal cell carcinoma (RCC) therapy with recombinant leukocyte interferon alpha A with and without vinblastin. ECCO-4, Fourth European conference on clinical oncology and cancer nursing, MadridGoogle Scholar
  10. 10.
    Belldegrun A, Muul LM, Rosenberg SA (1988) Interleukin 2 expanded tumor filtrating lymphocytes in human renal cancer: isolation, characterization and antitumor activity. Cancer Res 48:206Google Scholar
  11. 11.
    Beniers AJ, Peelen WP, Hendriks BT, Schalken JA, Debruyne FM (1988) Effect of alpha- and gamma-interferon and tumor necrosis factor on colony formation of two human renal tumor xenografts in vitro. Semin Surg Oncol 4(3):195Google Scholar
  12. 12.
    Bergerat P, Herbrecht R, Dufour P, Jacqmin D, Bollack C, Prevot G, Bailly G, de Garis S, Juraschek F, Oberling F (1988) Combination of recombinant interferon alpha-2a and vinblastine in advanced renal cell carcinoma. Cancer 62:2321Google Scholar
  13. 13.
    Bevilacqua MP, Pober JS, Majeau GR, Flers W, Cotran RS, Gimbrone MA Jr (1986) Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 83:4533Google Scholar
  14. 14.
    Bianchi R, Romani L, Puccetti P, Fioretti M (1988) Induction of tumor suppression and delayed-type footpad reaction by transfer of lymphocytes sensitized to a xenogenized tumor variant. Int J Cancer 42:71Google Scholar
  15. 15.
    Blackley SK, Lagada L, Woolfitt RA, Schellhammer PF (1988) Ex situ study of the effectiveness of enucleation in patients with renal cell carcinoma. J Urol 140:6Google Scholar
  16. 16.
    Bodrogi I, Baki M, Sinkovics I, Eckhardt S (1988) Ifosfamide chemotherapy of metastatic renal cell carcinoma. Sem in Surg Oncol 4:95Google Scholar
  17. 17.
    Borowitz MJ, Weiss MA, Bossen EH, and Metzger R (1986) Characterization of renal neoplasms with monoclonal antibodies to leukocyte differentiation antigens. Cancer 5:251Google Scholar
  18. 18.
    Bowcock AM, Kidd JR, Lathrop GM, Daneshvar L, May LT, Ray A, Sehgal PB, Kid KK, Cavalli-Sforza LL (1988) The human interferon-beta 2/hepatocyte stimulating factor/interleukin-6 gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8Google Scholar
  19. 19.
    Bradley EC, Louie AC, Paradise CM, Carlin DA, Bleyl CA, Groves ES, Rudolph AR (1989) Antitumor response in patients with metastatic renal cell carcinoma is dependent upon regimen intensity. Proc Ann Meet Am Soc Clin Oncol 8:A519Google Scholar
  20. 20.
    Brady LW (1983) Carcinoma of the kidney — role of radiotherapy. Semin Oncol 10:417Google Scholar
  21. 21.
    Brouckaert P, Spriggs DR, Demetri G, Kufe DW, Fiers W (1989) Circulating interleukin 6 during a continuous infusion of tumor necrosis factor and interferon gamma. J Exp Med 169:2257Google Scholar
  22. 22.
    Brown KD, Zurawski SM, Mosmann TR, Zurawski G (1989) A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol 142:679Google Scholar
  23. 23.
    Brubaker LH, Vogel CL, Einhorn LH, Birch R (1986) Treatment of advanced adenocarcinoma of the kidney with ICRF-1978: a southeastern cancer study group trial. Cancer Treat Rep 70:915Google Scholar
  24. 24.
    Brunetti I, Ardizzoni A, Falcone A, Sertoli MR, Rosso R, Guarneri D, Boccardo F, Currotto A, Martorana G (1987) Phase II study of recombinant alpha-2a interferon (RIFN 2a) plus vinblastine (VBL) in metastatic renal cell carcinoma (RCC). ECCO-4, Fourth European conference on clinical oncology and cancer nursing, MadridGoogle Scholar
  25. 25.
    Buckley NJ, Walther PJ, Das AK, Poulton SH (1989) Schedule-dependent enhanced lethality with combined administration of actinomycin D and tumor necrosis factor in mice. J Biol Response Mod 8:287Google Scholar
  26. 26.
    Budd GT, Osgood B, Barna B, Boyett JM, Finke J, Medendrop SV, Murthy S, Novak C, Sergi J, Tubbs R, Bukowski RM (1989) Phase I clinical trial of interleukin 2 and α-interferon: toxicity and immunological effects. Cancer Res 49:6432Google Scholar
  27. 27.
    Bukowski RM, Goodman P, Crawford ED, Sergi JS, Baker L, Neidhart J (1989) Phase II evaluation of recombinant interleukin-2 (RIL-2) in metastatic renal cell carcinoma (RCC):SWOG 8617. Proc Ann Meet Am Soc Clin Oncol 8:A556Google Scholar
  28. 28.
    Burgers JK, Marshall FF, Isaacs JT (1989) Enhanced anti-tumor effects of recombinant human tumor necrosis factor plus VP-16 on metastatic renal cell carcinoma in a xenograft model J Urol 142:160Google Scholar
  29. 29.
    Buzaid AC, Todd MB (1989) Therapeutic options in renal cell carcinoma. Semin Oncol 16 [Suppl 1]:12Google Scholar
  30. 30.
    Buzaid AC, Robertone A, Kissla C, Salmon SE (1987) Phase II study of interferon alpha-2a, recombinant (roferon-A) in metastatic renal cell carcinoma. J Clin Oncol 5:1083Google Scholar
  31. 31.
    Carswell EA, Old JL, Kassel L, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of human tumors. Proc Natl Acad Sci USA 72:3666Google Scholar
  32. 32.
    Catterall JF, Meseguer A (1989) The effects of sex steroids on renal gene expression. Semin Urol VII:252Google Scholar
  33. 33.
    Cetto GL, Franceschi T, Turrina G, Chiarion-Sileni V, Capelli MC, Bellini A, Paccagnella A, Bassetto MA, Molino AM, deSandre G (1988) Recombinant alpha-interferon and vinblastine in metastatic renal cell carcinoma: efficacy of low doses. Semin Surg Oncol 4:184Google Scholar
  34. 34.
    Charnetsky PS, Greisman RA, Salmon SE, Hersh EM, Scuderi P (1989) Increased peripheral blood leukocyte cytotoxic activity in cancer patients during the continuous intravenous administration of recombinant human tumor necrosis factor. J Clin Immunol 9:34Google Scholar
  35. 35.
    Chiou RK, Vessella RL, Eisson MK, Clayman RV, Gonzales-Campoy TA, Klicka MJ, Shafer RB, Lange PH (1985) Localization of human renal cell carcinoma xenografts with a tumor-preferential monoclonal antibody. Cancer Res 45:6140Google Scholar
  36. 36.
    Chiou RK, Vessella RL, Eisson MK, Palme DF, Lange PH (1987) Comparison of fresh tissue incubation assay and the in vivo localization of monoclonal antibodies to renal cell carcinoma. J Urol 137:1274Google Scholar
  37. 37.
    Chiou RK, Vessella RL, Limas C, Shafer RB, Elson MK, Arfman EW, Lange PH (1988) Monoclonal antibody-targeted radiotherapy of renal cell carcinoma using a nude mouse model. Cancer 61:1766Google Scholar
  38. 38.
    Cockburn AG, deVere White R (1984) Chemotherapy of advanced renal adenocarcinoma World J Urol 2:136Google Scholar
  39. 39.
    Cardon-Cardo C, Reuter VE, Finstad CL, Sheinfeld J, Lloyd KO, Fair WR, Melamed MR (1989) Blood group-related antigens in human kidney: modulation of Lewis determinants in renal cell carcinoma. Cancer Res 49:212Google Scholar
  40. 40.
    Creagan ET, Kovach JS, Moertel CG, Frytak S, Kvols LK (1988) A phase I clinical trial of recombination human tumor necrosis factor. Cancer 62:2467Google Scholar
  41. 41.
    Crickmore SP, Harris JE, Ellis TM, Braun DP, Cohen II, Bhoopalam N, Jassak PF, Cahill MA, Conzeri CL, Fisher RI (1989) A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusion. J Clin Oncol 7:276Google Scholar
  42. 42.
    Crivellari D, Tumolo S, Frustaci S, Galligioni E, Figoli F, Lo-Re G, Veronesi A, Monfardini S (1987) Phase II study of five-day continuous infusion of vinblastine in patients with metastatic renal-cell carcinoma. Am J Clin Oncol 10:231Google Scholar
  43. 43.
    Crump L III, Owen-Schaub LB, Grimm EA (1989) Synergy of human recombinant interleukin 1 with interleukin 2 in the generation of lymphokine-activated killer cells. Cancer Res 49:149Google Scholar
  44. 44.
    Damascelli B, Pizzocaro G, Soreafico C, Mauri M, Lutman L, Bonalumi B, Valvassori V, Marchianmo A, De Palo G, Bellegotti L, Del Nero A, Garbagnati F (1989) Improved survival in patients with metastatic renal cell carcinoma treated with continuous systemic infusion of FUDR. Proc Am Assoc Cancer Res 30:-A1030Google Scholar
  45. 45.
    deKernion JB, Berry D (1980) The diagnosis and treatment of renal cell carcinoma. Cancer 45:1947Google Scholar
  46. 46.
    deKernion JB, Ramming KP, Smith RB (1978) The natural history of metastatatic renal cell carcinoma: a computer analysis. J Urol 120:148Google Scholar
  47. 47.
    Dexues FH, Logothetis CJ, Sella A, Amato R, Ogden S, Kwan J, Striegel A (1989) Phase II study of continuous circadian infusion of 2-deoxy-5-fluorouridine (FUDR) for metastatic renal cell carcinoma (RCC). Proc Am Assoc Cancer Res 30:A1032Google Scholar
  48. 48.
    Diedrich H, Freund M, Schmoll HJ, Wilke H, von Wussow P (1987) Phase II trial of a combination with vinblastin (VBL), alpha-human-leukocyte interferon, and tamoxifen in advanced renal cell carcinoma (RCC). ECCO-4, Fourth European conference on clinical oncology and cancer nursing, MadridGoogle Scholar
  49. 49.
    Dijkmans R, Decock B, Heremans H, Van-Damme J, Billiau A (1989) Interferon-gamma is cytotoxic for normal mouse fibroblasts: enhancement by tumor necrosis factor and interleukin 1. Lymphokine Res 8:25Google Scholar
  50. 50.
    Dinarello CA (1989) Interleukin-1 and its biologically related cytokines. Adv Immunol 44:153Google Scholar
  51. 51.
    Dineen MK, Pastore RD, Emrich LJ, Huben RP (1988) Results of surgical treatment of renal cell carcinoma with solitary metastasis. J Urol 140:277Google Scholar
  52. 52.
    Droller MJ (1987) Biologic response modifiers in genitourinary neoplasia. Cancer 60 [Suppl]:635Google Scholar
  53. 53.
    Eisenhauer E, Wierbicki R, Venner P, Skillings J, Letendre F (1990) Phase II trial of recombinant tumor necrosis factor (rTNF) in patients with renal cell carcinoma (RCC). Proc Ann Meet Am Soc Clin Oncol 9:A539Google Scholar
  54. 54.
    Elson PJ, Kvols LK, Vogl SE, Glover DJ, Hahn RG, Trump DL, Carbone PP, Earle JD, Davis TE (1988) Phase II trials of 5-day vinblastine infusion (NSC 49842), L-alanosine (NSC 153353), acivicin (NSC 163501), and aminothiadiazole (NSC 4728) in patients with recurrent or metastatic renal cell carcinoma. Invest New Drugs 6:97Google Scholar
  55. 55.
    Fairlamb DJ (1981) Spontaneous regression of metastases of renal cancer: a report of two cases including the first recorded regression owing to irradiation of a dominant metastasis and review of the world literature. Cancer 47:2102Google Scholar
  56. 56.
    Fearon ER, Itaya T, Hunt B, Vogelstein B, Frost P (1988) Induction of immunogenic tumor variants by transfection with an foreign gene. Cancer Res 48:2975Google Scholar
  57. 57.
    Feng GS, Gray PW, Shepard HM, Taylor MW (1988) Antiproliferative activity of a hybrid protein between interferon-τ and tumor necrosis factor-β. Science 241:1501Google Scholar
  58. 58.
    Fidler IJ, Heicappell R, Saiki I, Grutter M, Horisberger M, Nuesch J (1987) Direct antiproliferate effects of recombinant human interferon-α B/D hybrids on human tumor cell lines. Cancer Res 47:2020Google Scholar
  59. 59.
    Figlin RA, Itri LM (1988) Anti-interferon antibodies: a perspective. Semin Hematol 25 [Suppl 3]:9Google Scholar
  60. 60.
    Figlin RA, deKernion LA, Mukamel E, Schnipper EF, Palleroni AV, DeVenezia LA, Sarna GP (1988) Recombinant leukocyte A interferon (rIFN alpha) antibody development in advanced renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 5:222Google Scholar
  61. 61.
    Figlin R, Citron M, Whitehead R, deKernion J, Desner M, Smith A, Jones G, Levitt D (1990) Low dose continuous infusion recombinant human interleukin-2 (rhIL-2) and Roferon; an active outpatient regimen for metastatic renal cell carcinoma (RCCa). Proc Ann Meet Am Soc Clin Oncol 9:A553Google Scholar
  62. 62.
    Fisher RI, Coltman CA Jr, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW, Wiernik P, McMannis JD, Weiss GR, Margolin KA (1988) Metastalic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med 108:518Google Scholar
  63. 63.
    Fojo AT, Shen DW, Mickley LA, Pastan IA, Gottesman MM (1987) Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug resistance gene. J Clin Oncol 5:1922Google Scholar
  64. 64.
    Fojo T, McAtee N, Allegra C, Bates S, Mickley L, Keiser H, Linehan M,Steinberg S, Tucker E, Goldstein L, Gottesman MM, Pastan I (1989) Use of quinidine and amiodarone to modulate multidrug resistance mediated by the MDR1 gene. Proc Ann Meet Soc Clin Oncol 8:A262Google Scholar
  65. 65.
    Foon KA (1989) Biological response modifiers: the new immunotherapy. Cancer Res 49:1621Google Scholar
  66. 66.
    Fossa SD (1988) Is interferon with or without vinblastin the “treatment of choice” in metastatic renal cell carcinoma. The Norwegian Radium Hospital's experience 1983–1986. Semin Surg Oncol 4:178Google Scholar
  67. 67.
    Fossa SD, de Garis ST, Heier MS, Flokkmann A, Lien HH, Salveson A, Moe B (1987) Recombinant interferon alpha-2a with or without vinblastin in metastatic renal cell carcinoma. Cancer 57:1700Google Scholar
  68. 68.
    Fowler JE Jr (1986) Failure of immunotherapy for metastatic renal cell carcinoma. J Urol 135:22Google Scholar
  69. 69.
    Frei E III, Spriggs D (1989) Tumor necrosis factor: still a promising agent. J Clin Oncol 7:291Google Scholar
  70. 70.
    Fritzberg AR (1989) Antibody targeted radiotherapy. Proc Am Assoc Cancer Res 30:648Google Scholar
  71. 71.
    Fujita T, Asano H, Naide Y, Ono Y, Oshima S, Suzuki K, Aso Y, Ariyoshi Y, Fukushima M, Ono K (1987) Antitumor effects of human lymphoblastoid interferon on advanced renal cell carcinoma. J Urol 139:256Google Scholar
  72. 72.
    Gams RA, Nelson O, Birch R (1986) Phase II evaluation of mitoxantrone in advanced renal cell carcinoma: a southeastern cancer study group. Cancer Treat Rep 70:921Google Scholar
  73. 73.
    Garnick MB, Reich SD, Maxwell B, Coval-Goldsmith S, Richie JP, Rudnick S (1988) A phase I/II study of recombinant interferon gamma in advanced renal cell carcinoma. J Urol 139:251Google Scholar
  74. 74.
    Gatanaga T, Noguchi K, Tanabe Y, Inagawa H, Soma G, Mizuno D (1989) Antitumor effect of systemic administration of novel recombinant tumor necrosis factor (rTNF-S) with less toxicity than conventional rTNF-alpha in vivo. J Biol Response Mod 8:278Google Scholar
  75. 75.
    Geboers AD, de-Mulder PH, Debruyne FM, Strijk SP, Damsma O (1988) Alpha and gamma interferon in the treatment of advanced renal cell carcinoma. Semin Surg Oncol 4:191Google Scholar
  76. 76.
    Giacomini P, Aguzzi A, Pestka S, Fisher PB, Ferrone S (1984) Modulation by DNA leukocyte (alpha) and fibroblast (beta) interferons of the expression and shedding of HLA and tumor associated antigens by human melanoma cells. J Immunol 133:1649Google Scholar
  77. 77.
    Glaves D, Huben RP, Weiss L (1988) Haematogenous dissemination of cells from renal adenocarcinomas. Br J Cancer 57:32Google Scholar
  78. 78.
    Glover D, Trump D, Kvols L, Elson P, Vogl S (1986) Phase II trial of misonidazole (MISO) and cyclophosphamide (CYC) in metastatic renal cell carcinoma. Int J Radiat Oncol Biol Phys 12:1405Google Scholar
  79. 79.
    Goldstein D, Sosman J, Hank J (1989) Repetitive weekly cycles of interleukin-2: outpatient treatment with a lower dose of IL-2 maintains heightened NK and LAK cell activity. Proc Annu Meet Am Soc Clin Oncol 8:193Google Scholar
  80. 80.
    Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Christ W, Brodeur GM, Lieber M, Cossman J, Gottesman MM, Pastan I (1989) Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81:16Google Scholar
  81. 81.
    Goodwin RG, Lupton S, Schmierer A, Hjerrild KJ, Jerzy R, Clevenger W, Gillis S, Cosman D, Namen AE (1989) Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci USA 86:302Google Scholar
  82. 82.
    Gosland MP, Lum BL, Sikic B (1989) Reversal by cefoperazone of resistance to etopside, doxorubicin, and vinblastin in multidrug resistant human sarcoma cells. Cancer Res 49:6901Google Scholar
  83. 83.
    Gottesman MM, Pastan I (1989) Clinical trials of agents that reverse multidrug-resistance. J Clin Oncol 7:409Google Scholar
  84. 84.
    Graham SD (1989) Immunotherapy of renal cell carcinoma. Semin in Urology VII:215Google Scholar
  85. 85.
    Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky L, Palladino MA, Nedwin GE (1984) Cloning and expresson of cDNA for human lymphotoxin, a lymphokine with tumor necrosis activity. Nature 312:721Google Scholar
  86. 86.
    Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) The lymphokine-activated killer cell phenomenon. Lysis of natural-killer resistant fresh solid human tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823Google Scholar
  87. 87.
    Grossman SA, Burch PA (1988) Quantitation of tumor response to anti-neoplastic therapy. Semin Oncol 15:441Google Scholar
  88. 88.
    Harris DT (1983) Hormonal therapy and chemotherapy of renal-cell carcinoma. Semin Oncol 10:422Google Scholar
  89. 89.
    Hartmann LC, Urba WJ, Steis RG, Smith JW II, Van der Molen L, Creekmore SP, Longo DL (1989) Hypothyroidism after interleukin-2 therapy. J Clin Oncol 7:686Google Scholar
  90. 90.
    Heicappell R, Schirrmacher V, von Hoegen P, Ahlert T, Appelhans B (1986) Prevention of postoperative metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effect. Int J Cancer 37:569Google Scholar
  91. 91.
    Heicappell R, Naito S, Creasy AA, Lin LS, Fidler IJ (1987) Antitumor activity of human recombinant tumor necrosis factor on human renal cell carcinoma cell lines derived from a single surgical specimen. J Immunol 138:1634Google Scholar
  92. 92.
    Heicappell R, Buszello H, Gabius H-J, Ackermann R (1990) Expression of endogenous carbohydrate receptors on human renal cell carcinoma cell lines with different metastatic propensity. Proc Am Assoc Cancer Res 31:A488Google Scholar
  93. 93.
    Heim ME, Schuster D, Schneider G, Ade N (1987) Combination therapy with recombinant alpha-2 interferon (IFN) and vinblastin (VB) in advanced renal cell carcinoma (RCC). ECCO-4, Fourth European conference on clinical oncology and cancer nursing, MadridGoogle Scholar
  94. 94.
    Herberman R (1989) Interleukin-2 therapy of human cancer: potential benefits versus toxocity. J Clin Oncol 7:1Google Scholar
  95. 95.
    Herberman RB, Ortaldo JR, Manovani A, Hobbs DS, Kung HF, Pestka S (1982) Effect of human recombinant interferon on cytotoxic activity of natural killer (NK) cells and monocytes. Cell Immunol 67:160Google Scholar
  96. 96.
    Herrmann F, Mertelsmann R (1989) Tumor necrosis factor [Tumornekrosefaktor]. Dtsch Med Wochenschr 114:312Google Scholar
  97. 97.
    Hienert G, Latal D, Rummelhardt S (1988) Urological aspects of surgical management for metastatic renal cell cancer. Semin Surg Oncol 4:137Google Scholar
  98. 98.
    Hirsch FW, Kraaz B, Lohr GW, Bross KJ (1988) Effectiveness and side effects of recombinant alpha-2a interferon in patients with metastatic hypernephroma. Onkologie 11:263Google Scholar
  99. 99.
    Horoszewicz JS, Murphy GP (1989) An assessment of the current use of human interferons in therapy of urological cancers. J Urol 142:1173Google Scholar
  100. 100.
    Inaba M, Fujikara R, Tshukagoshi S (1981) Restored in vitro sensitivity of adriamycin and vincristin-resistant P388 leukemia with reserpin. Biochem Pharmacol 30:2191Google Scholar
  101. 101.
    Jablons DM, Mule JJ, McIntosh JK, Sehgal PB, May LT, Huang CM, Rosenberg SA, Lotze MT (1989) IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol 142:1542Google Scholar
  102. 102.
    Jakubowski AA, Casper ES, Gabrilove JL, Templeton MA, Sherwin SA, Oettgen HF (1989) Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. J Clin Oncol 7:298Google Scholar
  103. 103.
    Javadpour N, Lalehzarian M (1988) A phase I–II study of high-dose recombinant human interleukin-2 in disseminated renal-cell carcinoma. Semin Surg Oncol 4:207Google Scholar
  104. 104.
    Kasid A, Director EP, Rosenberg SA (1989) Induction of endogenous cytokine-mRNA in circulating peripheral blood mononuclear cells by IL-2 administration to cancer patients. J Immunol 143:736Google Scholar
  105. 105.
    Katz SE, Schapira HE (1982) Spontaneous regression of genitourinary cancer — an update. J Urol 128:1Google Scholar
  106. 106.
    Kawakami Y, Rosenberg SA, Lotze MT (1988) Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma. J Exp Med 168:2183Google Scholar
  107. 107.
    Kellokumpu-Lehtinen P, Nordman E (1988) Combined interferon and vinblastine treatment of advanced melanoma and renal cell cancer. Cancer Detect Prev 12:523Google Scholar
  108. 108.
    Kempf RA, Grunberg SM, Daniels JR, Skinner DG, Venturi CL, Spiegel R, Neri R, Greiner JM, Rudnick S, Mitchell MS (1986) Recombinant interferon alpha-2 (INTRON A) in a phase II study of renal cell carcinoma. J Biol Response Mod 5:27Google Scholar
  109. 109.
    Kinney P, Triozzi P, Young D, Drago J, Behrens B, Wise H, Rinehart J (1988) Preliminary report of a phase II trial of interferon-beta serine in metastatic renal cell carcinoma. Proc Annu Meet Am Soc Clin Oncol 7:A627Google Scholar
  110. 110.
    Kish J, Ensley J, Al Sarraf M, Ratanatharathorn V, Karanes C, Galicky P (1986) Activity of serine substituted recombinant DNA β interferon (IFN-β) in patients with metastatic and recurrent renal cell cancer. Proc Am Assoc Cancer Res 27:184Google Scholar
  111. 111.
    Klein E (1989) The multidrug resistance gene in renal cell carcinoma. Semin Urol VII:207Google Scholar
  112. 112.
    Kochevar J (1987) A renal cell carcinoma neoplastic antigen detectable by immunohistochemistry is defined by a murine monoclonal antibody. Cancer 59:2031Google Scholar
  113. 113.
    Kozeny GA, Nicolas JD, Creekmore S, Sticklin L, Hano JE (1988) Effects of interleukin-2 immunotherapy on renal function. J Clin Oncol 6:1170Google Scholar
  114. 114.
    Kradin RL, Kurnick JT, Lazarus DS, Preffer FI, Dubinett SM, Pinto CE, Gifford J, Davidson E, Grove B, Callahan RJ, Strauss HW (1989) Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Lancet 1:577Google Scholar
  115. 115.
    Kreider JW, Bartlett GL, Butkiewicz BL (1984) Relationship of tumor leukocytic infiltration to host defense mechanism and prognosis. Cancer Metastasis Rev 3:53Google Scholar
  116. 116.
    Krigel R, Padavic K, Rudolph A, Comis R (1988) Phase II study of recombinant interleukin-2 (RIL-2) plus recombinant beta interferon (IFN-beta) in advanced renal cell carcinoma. Proc Annu Meet Am Soc Clin Oncol 7:A509Google Scholar
  117. 117.
    Krönke M, Hensel G, Schlüter C, Scheurich P, Schütze S, Pfitzenmeier K (1988) Tumor necrosis factor and lymphotoxin gene expression in human tumor cell lines. Cancer Res 48:5417Google Scholar
  118. 118.
    Krosnick JA, Mulé JJ, McIntosh JJ, Rosenberg SA (1989) Augmentation of antitumor efficacy by the combination of recombinant tumor necrosis factor and chemotherapeutic agents in vivo. Cancer Res 49:3729Google Scholar
  119. 119.
    Krown S (1987) Interferon treatment of renal cell carcinoma. Current status and future prospects. Cancer 59 [Suppl]:647Google Scholar
  120. 120.
    Kuebler J, Brown T, Goodman P, Crawford D, Reutz C, Knight W, Kish J (1989) Continuous infusion recombinant gamma interferon (CIR-GIFN) for metastatic renal cell carcinoma (RCC). Proc Annu Meet Am Soc Clin Oncol 8:A544Google Scholar
  121. 121.
    Kurth K, Marquet R, Zwartendijk J, Warnaar SD (1987) Autologous anticancer antigen preparation for specific immunotherapy in advanced renal cell carcinoma. Eur Urol 13:103Google Scholar
  122. 122.
    Lee RL, Lotze ML, Skibber JM, Tucker E, Bonow RO, Ognibene FP, Carrasquillo JA, Shelhamer JA, Parillo JE, Rosenberg SA (1989) Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 7:7Google Scholar
  123. 123.
    Leventhal B (1988) An overview of clinical trials in oncology. Semin Oncol 15:414Google Scholar
  124. 124.
    Lindemann A, Hoeffken K, Schmidt RE, Diehl V, Kloke O, Gamm H, Hayungs J, Oster W, Boehm M, Franks CR (1989) A multicenter trial of interleukin-2 and low-dose cyclophosphamide in highly chemotherapy resistant malignancies. Cancer Treat Rev 16[Suppl A]:53Google Scholar
  125. 125.
    Lindemann A, Monson JRT, Stahel RA, Clabrese F, Ludwig C, Osterwalder B, Decoster G, Mertelsmann R (1990) “Low intensity” combination treatment with r-interleukin-2 (rh-IL-2) and r-interferon alfa-2a (rh-IFN-a-2a) in renal cell carcinoma. A multicenter phase II trial. Proc Annu Meet Am Soc Clin Oncol 9:A584Google Scholar
  126. 126.
    Ling V, Kartner N, Sudo T, Siminovitch L, Riordan JR (1983) Multidrug resistance phenotype in Chinese hamster ovary cells. Cancer Treat Rep 67:869Google Scholar
  127. 127.
    Lipton A, Harvey H, Hirsh M. Hopper K, Givant E, Levitt D, Zeffren J, Jones G (1990) Treatment of metastatic renal cell carcinoma with infusion of interleukin-2 and intramuscular interferon alfa-2a. Proc Annu Meet Am Soc Clin Oncol 9:A534Google Scholar
  128. 128.
    Luner SJ, Ghose T, Chatterjee S, Cruz HN, Belitsky P (1986) Monoclonal antibodies to kidney and tumor-associated surface antigens of human renal cell carcinoma. Cancer Res 46:5816Google Scholar
  129. 129.
    Lupera H, Court BH, Theodore C, Wibault P, Ghosn M, Droz JP (1989) Phase II trial of combination chemotherapy with dacarbazine, cyclophosphamide, cisplatin, doxorubicin, and vindesine (DECAV) in advanced renal cell cancer. Urology 34:281Google Scholar
  130. 130.
    Maennel DN, Moore RN, Mergenhagen SE (1980) Macrophages as a source of tumoricidal activity (tumor-necrotizing factor). Infect Immunol 30:523Google Scholar
  131. 131.
    Maor MH, Frias AE, Oswald MJ (1988) Palliative radiotherapy for brain metastases in renal carcinoma. Cancer 62:1912Google Scholar
  132. 132.
    Margolin KA, Rayner AA, Hawkins MJ, Atkins MB, Dutcher JP, Fisher RI, Weis GR, Doroshow JH, Jaffe HS, Roper M, Parkinson DR, Wiernik PH, Creekmore SP, Boldt DH (1989) Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol 7:486Google Scholar
  133. 133.
    Markowitz A, Talpaz M, Lee K, Parkinson D, Doig R, Rothberg J, Levitt D, Gutterman J (1989) Phase I–II study of recombinant interleukin-2 (RIL-2) plus recombinant interferon-alpha 2a (RIFN-alpha) in renal cell carcinoma (RCC). Proc Meet Am Soc Clin Oncol 8:A568Google Scholar
  134. 134.
    Marshall FF, Walsh PC (1984) In situ management of renal tumors: renal cell carcinoma and transitional cell carcinoma. J Urol 131:1045Google Scholar
  135. 135.
    Marshall FF, Taxy JB, Fishman EK, Chang R (1986) The feasibility of surgical enucleation for renal cell carcinoma. J Urol 135:231Google Scholar
  136. 136.
    Marshall ME, Butler K, Dickson L, Phillips B, McComell W, Macdonald JS (1989) Treatment of metastatic renal cell carcinoma with low dose interleukin-2 and lymphokine-activated killer cells. Proc Ann Meet Am Soc Clin Oncol 8:A525Google Scholar
  137. 137.
    Marumo K, Muraki J, Ueno M, Tachibana M, Deguchi N, Baba S, Jitsukawa S, Hata M, Tazaki H (1989) Immunologic study of human recombinant interleukin-2 (low-dose) in patients with advanced renal cell carcinoma. Urology 33:219Google Scholar
  138. 138.
    McCune CS (1983) Immunologic therapies of kidney carcinoma. Semin Oncol 10:431Google Scholar
  139. 139.
    McGovern L (1975) Spontaneous regression of human melanoma. Pathology 7:91Google Scholar
  140. 140.
    McIntosh JK, Jablons DM, Mule JJ, Nordan RP, Rudikoff S, Lotze MT, Rosenberg SA (1989) In vivo induction of IL-6 by administration of exogenous cytokines and detection of de nove serum levels of IL-6 in tumor-bearing mice. J Immunol 143:162Google Scholar
  141. 141.
    Mitchell M (1988) Combining chemotherapy with biological response modifiers in treatment of cancer. J Natl Cancer Inst 80:1445Google Scholar
  142. 142.
    Mitchie HR, Manogue KR, Spriggs DR, Revhaug A, O'Dwyer S, Dinarello CA, Cerami A, Wolff SM, Wilmore DW (1988) Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318:1481Google Scholar
  143. 143.
    Merigan T (1988) Human interferon as a therapeutic agent. N Engl J Med 318:1458Google Scholar
  144. 144.
    Mittelman C, Puccio C, Ahmed T, Arnold P, Levitt D, Arlin Z (1990) Phase II trial of recombinant interleukin-2 (IL-2) and roferon A (IFN) in patients (PTS) with advanced renal cell carcinoma. Proc Annu Meet Am Soc Clin Oncol 9:A736Google Scholar
  145. 145.
    Montie JE, Bukowski RM, Lee RJ, Straffon RA, Stewart BH (1982) A critical review of immunotherapy of disseminated renal adenocarcinoma. J Surg Oncol 21:5Google Scholar
  146. 146.
    Moritz T, Niederle N, Baumann J, May D, Kurschel E, Osieka R, Kempeni J, Schlick E, Schmidt CG (1989) Phase I study of recombinant human tumor necrosis factor alpha in advanced malignant disease. Cance Immunol Immunother 29:144Google Scholar
  147. 147.
    Mukaida N, Shiroo M, Matsushima K (1987) Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol 143:1366Google Scholar
  148. 148.
    Muss HB, Constanzi JJ, Leavitt R, Williams RD, Kempf RA, Pollard R, Ozer H, Zekan PJ, Grunberg SM, Mitchell MS (1987) Recombinant alpha interferon in renal cell carcinoma: a randomized trial of two routes of administration. J Clin Oncol 5:286Google Scholar
  149. 149.
    Nagakura K, Haykawa M, Hata M, Nakamura H (1987) 1,25-Dihydroxyvitamin D3 receptors and their relationship to histological features in renal cell carcinoma. J Urol 137:1300Google Scholar
  150. 150.
    Naito S, von Eschenbach A, Giavazzi R, Fidler IJ (1986) Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res 46:4109Google Scholar
  151. 151.
    Neidhardt JA (1986) Interferon therapy for the treatment of renal cancer. Cancer 58 [Suppl]:1696Google Scholar
  152. 152.
    Neidhardt JA, Murphy SG, Hennick LA, Wise HA (1980) Active specific immunotherapy of stage IV renal carcinoma with aggregated tumor antigen adjuvant. Cancer 46:1128Google Scholar
  153. 153.
    Nelson KA, Wallenberg JC, Todd MB (1989) High-dose intrevenous therapy with beta interferon in patients with renal cell carcinoma. Proc Am Assoc Cancer Res 30:A1034Google Scholar
  154. 154.
    O'Garra A (1989) Interleukins and the immune system 1. Lancet I:943Google Scholar
  155. 155.
    O'Garra A (1989) Interleukins and the immune system 2. Lancet I:1003Google Scholar
  156. 156.
    Oliver RTDJ (1987) Unexplained “spontaneous” regression and its relevance to the clinical behavior of renal cell carcinoma and its response to interferon. Proc Annu Meet Am Soc Clin Oncol 6:98Google Scholar
  157. 157.
    Oosterwijk E, Fleuren GJ, Jonas U, Zwartendijk J, te Velde J, Warnaar SO (1984) The expression of renal antigens in renal cell carcinoma. World J Urol 2:156Google Scholar
  158. 158.
    Oosterwijk E, Ruiter DJ, Wakka JC, Huiskens JW, Meij VD, Jonas U, Fleuren G-J, Zwartendijk J, Hoedemaeker Ph, Warnaar SO (1986) Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma. Am J Pathol 123:301Google Scholar
  159. 159.
    Oosterwijk E, Ruiter DJ, Hoedemaker PJ, Pauwels EK, Jonas U, Zwartendijk J, Warnaar SO (1986) Monoclonal antibody G 250 recognizes a determinant present in renal cell carcinoma and absent from normal kidney. Int J Cancer 38:489Google Scholar
  160. 160.
    Ortaldo JR, Longo DL (1988) Human natural lymphocyte effector cells, definition, analysis of activity, and clinical effectiveness. J Natl Cancer Inst 80:999Google Scholar
  161. 161.
    Osband ME, Lavin PT, Babayan RK, Graham S, Lamm DL, Parker B, Sawczuk I, Ross S, Krane RJ (1990) Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma. Lancet I:994Google Scholar
  162. 162.
    Otto U, Huland H, Schneider A, Denkhaus H (1988) Treatment of patients with metastatic renal cell carcinoma: results of two clinical phase II studies with alpha-2-interferon versus alpha-2 interferon plus vinblastin or gamma interferon in 55 patients. J Urol 133:329A, A904Google Scholar
  163. 163.
    Otto U, Conrad S, Schneider AW, Kempeni J, Schlick E, Klosterhalfen H (1990) Combined therapy with TNF-alpha and IFN-alpha 2a: a promising approach to treatment of metastatic renal cell carcinoma. Proc Ann Meet Am Soc Clin Oncol 8:A573Google Scholar
  164. 164.
    Philip T, Stoter G, Jasmin C, Fossa SD, Symann M, Israel L, Rugarli C, Bijman JT, Palmer P, Franks CR (1989) Recombinant human interleukin-2 with or without LAK cells in metastatic renal cell carcinoma. Proc Ann Meet Am Soc Clin Oncol 8:A507Google Scholar
  165. 165.
    Phillips JH, Gemlo BT, Myers WW, Rayner AA, Lanier LL (1987) In vivo and in vitro activation of natural killer cells in advanced cancer patients undergoing combined recombinant interleukin-2 and LAK cell therapy. J Clin Oncol 5: 1933Google Scholar
  166. 166.
    Piot G, Droz JP, Theodore C, Ghosn M, Rouesse J, Amiel JL (1988) Phase II trial with high-dose elliptinium acetate in metastatic renal cell carcinoma. Oncology 45: 371Google Scholar
  167. 167.
    Porzsolt F, Messerer D, Hautmann R, Gottwald A, Sparwasser H, Stockamp K, Aulitzky W, Moormann JG, Schumacher K, Rasche H (1988) 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 114: 95Google Scholar
  168. 168.
    Puri RK, Travis WA, Rosenberg SA (1989) Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1α in vivo. Cancer Res 49: 767Google Scholar
  169. 169.
    Richards JM, Barker E, Latta J, Ramming K, Vogelzang NJ (1988) Phase I study of weekly 24-hour infusions of recombinant human interleukin-2. J Natl Cancer Inst 80: 1325Google Scholar
  170. 170.
    Quesada J (1988) Biologic response modifiers in the therapy of metastatic renal cell carcinoma. Semin Oncol 15: 396Google Scholar
  171. 171.
    Quesada JR, Rios A, Swanson D, Trown P, Gutterman JU (1985) Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma. J Clin Oncol 3: 1522Google Scholar
  172. 172.
    Quesada JR, Kurzrock R, Sherwin SA, Gutterman JU (1987) Phase II studies of recombinant human interferon gamma in metastatic renal cell carcinoma. J Biol Resp Modif 6: 20Google Scholar
  173. 173.
    Quesada J, Evans L, Saks SR, Gutterman JU (1988) Recombinant interferon alpha and gamma in combination as treatment for metastatic renal cell carcinoma. J Biol Response Mod 7: 234Google Scholar
  174. 174.
    Rauschmeier HA (1988) Immunotherapy of metastatic renal cancer. Semin Surg Oncol 4: 169Google Scholar
  175. 175.
    Recombinant human interferon gamma (S-6810) research group on renal cell carcinoma (1987) Phase II study of recombinant human interferon gamma (S.6810) on renal cell carcinoma. Summary of two collaborative studies. Cancer 60: 929Google Scholar
  176. 176.
    Redman BG, Flaherty L, Chou TH, Martino S, Al Katib A, Kaplan J, Valdivieso M (1989) Phase I trial of combination therapy with recombinant interleukin-2 (IL-2) and recombinant interferon-gamma in patients with cancer. Proc Annu Meeting Am Soc Clin Oncol 8: A734Google Scholar
  177. 177.
    Rieden K, Adolph J, Lellig U, zum Winkel K (1989) Radiation effect on bone metastases as a function of frequency, localization and histology of primary tumor (in German). Strahlenther Onkol 165: 380Google Scholar
  178. 178.
    Rinehart J, Neidhart J, Meyer N, Hine C, Young D (1985) Phase I trial of recombinant beta-interferon (IFN) in metastatic renal cell carcinoma. Preliminary report. Proc Annu Meet Am Soc Clin Oncol 4: 224Google Scholar
  179. 179.
    Rosenberg S (1989) Clinical immunotherapy studies in the surgery branch of the U.S. National Cancer Institute: brief review. Cancer Treat Rev 16 [Suppl A]: 115Google Scholar
  180. 180.
    Rosenberg SA, Spiess P, Lanafriere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233: 1318Google Scholar
  181. 181.
    Rosenberg SA, Lotze MT, Muul LM, Chan AE, Avis FP, Leitman S, Marston Linehan W, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316: 889Google Scholar
  182. 182.
    Rosenberg SA, Schwarz SL, Spiess PJ (1988) Combination immunotherapy for cancer: synergistic antitumor interactions of interleukin-2, alpha interferon, and tumor infiltrating lymphocytes. J Natl Cancer Inst 80: 133Google Scholar
  183. 183.
    Rosenstein M, Ettinghausen SE, Rosenberg SA (1986) Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. J Immunol 137: 1735Google Scholar
  184. 184.
    Rubin JT, Elwood LJ, Rosenberg SA, Lotze MT (1989) Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. Cancer Res 49: 7086Google Scholar
  185. 185.
    Sahasrabudhe DM, deKernion JB, Pontes JE, Ryan DM, O'Donnell RW, Marquis DM, Mudholkar GS, McCune CS (1986) Specific immunotherapy with suppressor function inhibition of metastatic renal cell carcinoma. J Biol Response Mod 5: 581Google Scholar
  186. 186.
    Salmon SS, Liu R (1989) Effects of granulocyte-macrophage colony-stimulating factor on in vitro growth of human solid tumors. J Clin Oncol 7: 1346Google Scholar
  187. 187.
    Schärfe T, Klippel KF, Jacobi GH, Hohenfellner R (1983) Tumor specific immunotherapy for metastatic renal cell carcinoma. 78th Annual Meeting of the American Urological Association (abstract)Google Scholar
  188. 188.
    Schärfe T, Störkel ST, Yokohama, Kaltwasser R, Thüroff J, Jacobi GH, Hohenfellner R (1988) Tumor-specific antigen for human renal cell carcinoma. Eur Urol 14: 464Google Scholar
  189. 189.
    Scheithauer W, Theyer G, Zechner O, Ludwig H (1988) Experiences with continuous intraarterial administration of recombinant interferon alpha-2C (rIFN-alpha 2) for treatment of patients with advanced transitional cell bladder cancer. J Biol Regul Homeost Agents 2: 67Google Scholar
  190. 190.
    Scher HI, Yagoda A, Ahmed T, Hollander P, Watson RC (1984) Phase II trial of 10-deazaminopterin for advanced hypernephroma. Anticancer Res 4: 409Google Scholar
  191. 191.
    Scher HI, Yagoda A, Ahmed T, Budman D, Sordillo P, Watson RC (1985) Phase-II trial of 4-demethoxydaunorubicin (DMDR) for advanced hypernephroma. Cancer Chemother Pharmacol 14: 79Google Scholar
  192. 192.
    Schirmer WJ, Schirmer JM, Fry DE (1982) Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia. Arch Surg 124: 445Google Scholar
  193. 193.
    Schirrmacher V (1985) Cancer metastasis: experimental approaches, theoretical concepts, and impacts for treatment strategies. Adv Cancer Res 434: 1Google Scholar
  194. 194.
    Schirrmacher V, Fogel M, Russmann E, Bosslet K, Altevogt P, Beck L (1982) Antigenic variation in cancer metastasis: immune excape versus immune control. Cancer Metastatis Rev 1: 241Google Scholar
  195. 195.
    Schwartz R, Momburg F, Moldenhauer G, Doerken B, Schirrmacher V (1985) Induction of HLA class II antigen expression by interferon gamma. Int J Cancer 35: 245Google Scholar
  196. 196.
    Sculier JP (1989) The medical treatment of renal cancer in adults. Rev Med Brux 10: 190Google Scholar
  197. 197.
    Sertoli MR, Brunetti I, Ardizzoni A, Falcone A, Guarneri D, Boccardo F, Martorana G, Curotto A, Sicignano A, Rosso R (1989) Recombinant alpha-2a interferon plus vinblastine in the treatment of metastatic renal cell carcinoma. Am J Clin Oncol 12: 43Google Scholar
  198. 198.
    Silverberg E (1987) Statistical and epidemiological data on urologic cancer. Cancer 60 [Suppl]: 692Google Scholar
  199. 199.
    Sosman JA, Kohler PC, Hank J, Moore KH, Berchhofer R, Storer B, Sondel PM (1988) Repetitive weekly cycles of recombinant human interleukin-2: responses of renal carcinoma with acceptable toxicity. J Natl Cancer Inst 80: 60Google Scholar
  200. 200.
    Sosman JA, Kohler PC, Hank J, Moore KH, Berchhofer R, Storer B, Sondel PM (1988) Repetitive weekly cycles of interleukin-2. II. Clinical and immunologic effects of dose, schedule, and addition of indomethacin. J Natl Cancer Inst 80: 1451Google Scholar
  201. 201.
    Steinmetz T, Schaadt M, Gahl R, Schenk V, Diehl V, Pfreundschuh M (1988) Phase I study of 24-hour continuous intravenous infusion of recombinant human tumor necrosis factor. J Biol Response Mod 7: 417Google Scholar
  202. 202.
    Stephens RL, Kirby R, Crawford ED, Bukowski R, Rivkin SE, O'Bryan RM (1986) High dose AZQ in renal cancer. A southwest oncoloy group phase II study. Invest New Drugs 4: 57Google Scholar
  203. 203.
    Sterman D, Bajorin D, Reichman B, Sternberg C, Groeger J, Kolitz J, Reich L, Scher H, Cody B, Gold J (1989) Infectious complications of interleukin-2 (IL-2) therapy in patients with renal cell carcinoma (RCC) and melanoma (MEL). Proc Annu Meet Am Soc Clin Oncol 8: A747Google Scholar
  204. 204.
    Stewart DJ, Futter N, Irvine A, Danjoux C, Moors D (1987) Mitomycin-C and metronidazole in the treatment of advanced renal-cell carcinoma. Am J Clin Oncol 10: 520Google Scholar
  205. 205.
    Sugarman BR, Aggarwal BB, Hass PE, Figari IS, Palladinom MA, Sheppard HM (1985) Recombinant tumor necrosis factor alpha: effects on proliferation of normal and transformed cells in vitro. Science 230: 943Google Scholar
  206. 206.
    Taguchi T (1988) Phase I study of recombinant human tumor necrosis factor (rHU-TNF:PT-050). Cancer Detect Prev 12: 561Google Scholar
  207. 207.
    Tallberg T, Tykkä H (1986) Specific active immunotherapy in advanced renal cell carcinoma: a clinical longterm follow-up study. World J Urol 3: 234Google Scholar
  208. 208.
    Thompson JA, Lee DL, Lindgren CG, Benz LA, Collins C, Levitt D, Fefer A (1988) Influence of dose and duration of infusion on interleukin-2 on toxicity and immunomodulation. J Clin Oncol 6: 669Google Scholar
  209. 209.
    Thompson JA, Lee DJ, Lindgren CG, Benz LA, Collins C, Shuman WP, Levitt P, Fefer A (1989) Influence of schedule of interleukin 2 administration on therapy with interleukin 2 and lymphocyte activated killer cells. Cancer Res 49: 235Google Scholar
  210. 210.
    Topalian SL, Salomon D, Avis FP, Chan AE, Freerksen DL, Linehan WM, Lotze MT, Robertson CN, Seipp CA, Simon P, Simpson CG, Rosenberg SA (1988) Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol 6: 839Google Scholar
  211. 211.
    Tovey MG (1989) Expression of the genes of interferons and other cytokines in normal and diseased tissues of man. Experientia 45: 526Google Scholar
  212. 212.
    Tsuruo T, Iida H, Tsugokoshi S (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41: 1967Google Scholar
  213. 213.
    Tsuruo T, Iida H, Kitatani S, Yokota K, Tsukagosh S, Sakurai Y (1984) Effects of quinidine and related compounds on cytotoxicity and cellular accumulation of vincristine and adriamycin in drug resistant tumor cells. Cancer Res 44: 4304Google Scholar
  214. 214.
    Ueda R, Ogata SI, Morrissey DM, Finstad CL, Skudlarek J, Whitmore WF, Oettgen HF, Lloyd KO, Old LJ (1981) Cell surface antigens of human renal cancer defined by mouse monoclonal antibodies: identification of tissue-specific kidney glycoproteins. Proc Natl Acad Sci USA 78: 5122Google Scholar
  215. 215.
    van der Poll T, Büller H, ten Cate H, Wortel C, Bauer KA, van Deventer SJH, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW (1990) Activation of coagulation after administration of tumor necrosis to normal subjects. N Engl J Med 322: 1622Google Scholar
  216. 216.
    van Dijk J, Warnaar SO, van Eendenburg JDH, Thienpont M, Braakman E, Boot JHA, Fkeuren GJ, Boildhues RHL (1989) Induction of tumor-cell lysis by bi-specific monoclonal antibodies recognizing renal-cell carcinoma and CD3 antigen. Int J Cancer 43: 344Google Scholar
  217. 217.
    van Oosterom AT, Denis L (1986) Renal adenocarcinoma. In: Slevin ML, Staquet ML (eds) Randomized trials in cancer: a critical review by site. Raven, New York, p 661Google Scholar
  218. 218.
    van Snick J, Goethal A, Renauld JC, van Roost E, Uyttenhove C, Rubira MR, Moritz RL, Simpson RJ (1989) Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40). J Exp Med 169: 363Google Scholar
  219. 219.
    Venditti JM (1982) The model's dilemma. In: Fidler IJ, White RJ (eds) Design of models for testing cancer therapeutic agents. Van Nostrand Reinhold, New York, p 80Google Scholar
  220. 220.
    Vessella RL, Moon TD, Chiou R-K, Nowak JA, Arfman EA, Palme DF, Peterson GA, Lange PH (1985) Monoclonal antibodies to human renal cell carcinoma. Recognition of shared and restricted tissue antigens. Cancer Res 45: 6331Google Scholar
  221. 221.
    Vilcek J, Palombella VJ, Hendriksen-DeStefano D, Swenson C, Feiman R, Hirai M, Tsujimoto M (1986) Fibroblast growth enhancing activity of tumor necrosis factor and its relationship to other polypeptide growth factors. J Exp Med 163: 632Google Scholar
  222. 222.
    van Hoegen P, Heicappell R, Griesbach A, Altevogt P, Schirrmacher V (1989) Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. III. Postoperative activation of tumor specific CTLP from mice with metastases requires stimulation with the specific antigen plus additional signals. Invasion and Metastasis 9: 117Google Scholar
  223. 223.
    van Roemeling R, Rabatin JT, Fraley EE, Hrushesky WJM (1988) Progressive metastatic renal cell carcinoma controlled by continuous 5-fluoro-2-deoxyuridine infusion. J Urol 139: 259Google Scholar
  224. 224.
    Wadler S, Einzig AI, Dutcher JP, Ciobanu N, Landau L, Wiernik PH (1988) Phase II trial of recombinant alpha-2b-interferon and low-dose cyclophosphamide in advanced melanoma and renal cell carcinoma. Am J Clin Oncol 11: 55Google Scholar
  225. 225.
    Wang J, Walle A, Gordon B, Novogrodsky A, Suthanthiran M, Rubin AL, Morrison H, Silver RT, Stenzel KH (1987) Adoptive immunotherapy for stage IV renal cell carcinoma: a novel protocol utilizing periodate and interleukin-2-activated autologous leukocytes and continuous infusions of low-dose interleukin-2. Am J Med 83: 1016Google Scholar
  226. 226.
    Weinerman BH, Eisenhauer EA, Besner JG, Coppin CM, Stewart D, Band PR (1986) Phase II study of lonidamine in patients with metastatic renal cell carcinoma: a national cancer institute of Canada clinical trials group study. Cancer Treat Rep 70: 751Google Scholar
  227. 227.
    West WH, Taeur KW, Yanelli JTR, Marshall GD, Orr DW, Thurman GB, Oldham RK (1987) Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of renal cancer. N Engl J Med 316: 898Google Scholar
  228. 228.
    Whitehead RP, Ward DL, Hemingway LL, Hemstreet GP III (1987) Effect of subcutaneous recombinant interleukin 2 in patients with disseminated renal cell carcinoma. Proc Annu Meet Am Soc Clin Oncol 6: A947Google Scholar
  229. 229.
    Wiedenmann B, Reichardt P, Rath U, Theilmann L, Schule B, Ho AD, Schlick E, Kempeni J, Hunstein W, Kommerell B (1989) Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas. J Cancer Res Clin Oncol 5: 189Google Scholar
  230. 230.
    Wilson DE, Birchfield GR, Hejazi JS, Ward JH, Samlowski W (1989) Hypocholesterinemia in patients treated with recombinant interleukin-2: appearance of remnant-like lipoproteins. J Clin Oncol 7: 1573Google Scholar
  231. 231.
    Wunderlich JR, Garrido MA, Valdayo M, Winkler DF, Titus JA, Perez P, Quian J, Segal DM (1989) Targeting human T cells with bispecific antibodies to react with human tumors growing in immunodeficient mice. Proc Am Assoc Cancer Res 30: 647Google Scholar
  232. 232.
    Yagoda A (1989) Chemotherapy of renal cell carcinoma. Semin Urol VII: 199Google Scholar
  233. 233.
    Ziegelbaum MM, Montie JE, Finke JH, Pontes EJ, Tubbs R, Lewis I (1989) In vitro activation of lymphocytes by interleukin 2 in patients with renal cell carcinoma. Urology XXXIII: 106Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • R. Heicappell
    • 1
  • R. Ackermann
    • 1
  1. 1.Department of UrologyHeinrich-Heine-UniversityDüsseldorfGermany

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