Advertisement

Biotherapy

, Volume 8, Issue 3–4, pp 229–241 | Cite as

Cytokines in animal models of cancer

  • Frances Burke
  • Frances R. Balkwill
Article

Abstract

Cytokines are a complex family of mediators that play a wide role in development, immunity, inflammation and tissue repair. Their use in therapy is still in its infancy and animal models have a key role to play in optimizing doses and schedules. Whilst xenogeneic and syngeneic transplantable systems have traditionally been used to look at the effects of cytokines in tumour models, oncogene transgenic mice prone to develop cancer, may now have a role to play. Moreover, gene therapy has allowed the investigation of ectopically expressed high and continous levels of cytokines. We will attempt to review the literature on the effect of cytokines and their combinations in these models of cancer.

Key words

animal models cancer cytokines interferons interleukins 

Abbreviations

CML

chronic myeloid leukemia

5-FU

5-fluoruracil

FLC

Friend leukemia cells

i.p.

intraperitoneal

IFN

interferon

IL

interleukins

LAK

lymphokine activated killer

s.c

subcutaneous

SCCHN

human squamous cell carcinoma of the head and neck

TNF

tumour necrosis factor

PEG

polyethylene-glycol

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mattern J, Bak M, Hahn EW, Volm M. Human tumor xenografts as model for drug testing. Cancer Metastasis Rev 1988; 7: 263–284.PubMedGoogle Scholar
  2. 2.
    Fiebig HH. Comparison of tumour responses in nude mice and in patients. In: Winograd PMJ, Pinedo H. M. ed: Human Tumour Xenografts in Anticancer Drug Development 1988. Springer-Verlag, Berlin, p 25–30.Google Scholar
  3. 3.
    Fidler IJ. Rationele and methods for use of nude mice to study the biology and therapy of human cancer metastases. Cancer Metastasis Rev 1986; 5: 29–49.PubMedGoogle Scholar
  4. 4.
    Brinster RL, Chen HY, Messing A, Van Dyke T, Levine AJ, Palmiter RD. Transgenic mice harboring SV40 T-Antigen genes develop characteristic brain tumors. Cell 1984; 37: 367–379.PubMedGoogle Scholar
  5. 5.
    Thomas H, Balkwill FR. Oncogene transgenic mice as therapeutic models in cancer research. Eur J Cancer 1994; 4: 533–7.Google Scholar
  6. 6.
    Miller AR, McBride WH, Hunt K, Economou JS. Cytokinemediated gene therapy for cancer. Ann Surg Oncol 1994; 1(5): 436–50.PubMedGoogle Scholar
  7. 7.
    Foa R, Cignetti A, Riera L, Gillio Tos A, Guarini A. Cytokine gene therapy in oncology. Folia Biol Praha 1994; 40 (1–2): 37–48.PubMedGoogle Scholar
  8. 8.
    Golumbek PT, Azhari R, Jaffee EM, Levitsky HI, Lazenby A, Leong K, Pardoll DM. Controlled release, biodegradable cytokine depots: A new approach in cancer vaccine design. Cancer Res 1993; 53: 5841–5844.PubMedGoogle Scholar
  9. 9.
    Crane JL, Glasgow LA, Kern ER, Youngner JS. Inhibition of murine osteogenic sarcomas by treatment with type I or type II interferon. JNCI 1978; 61: 871–873.PubMedGoogle Scholar
  10. 10.
    Balkwill FR, Taylor-Papadimitriou J, Fantes KH, Sebesteny A. Human lymphoblastoid interferon can inhibit the growth of human breast cancer xenografts in athymic (nude) mice. Eur J Cancer 1980; 16: 569–573.PubMedGoogle Scholar
  11. 11.
    Balkwill FR, Moodie EM, Freedman V, Fantes KH. Human interferon inhibits the growth of established human breast tumours in the nude mouse. Int J Cancer 1982; 30: 231–235.PubMedGoogle Scholar
  12. 12.
    Balkwill FR. Antitumour effects of interferons in animals. Interferon 4: in vivo & clincial studies, 1985, pp. 23–45.Google Scholar
  13. 13.
    Balkwill FR, Goldstein L, Stebbing N. Differential action of six human interferons agains two human carcinomas growing in nude mice. Int J Cancer 1985; 35: 613–617.Google Scholar
  14. 14.
    Brosjo O, Bauer HCF, Brostrom L-A, Nilssone U, Nilsson OS, Reinholt HS, Tribukait B. Influence of human a-interferon on four human osteosarcoma xenografts in nude mice. Cancer Res 1985; 45: 5598–5602.PubMedGoogle Scholar
  15. 15.
    Brosjo O, Bauer HCF, Brostrom L-A, Nilsson OS, Reinholt FP, Tribukait B. Growth inhibition of human osteosarcomas in nude mice by human interferon-alpha:signiflcance of growth & tumour differation. Cancer Res 1987; 47: 258–262.PubMedGoogle Scholar
  16. 16.
    Hofmann V, Groscurth P, Morant R, Cserhati M, Honegger HP, von Hochstetter A. Effects of leukocyte interferon (E. coli) on human bone sarcoma growthin vitro and in the nude mouse. Eur J Cancer Clin Oncol 1985; 21 (7): 859–63.PubMedGoogle Scholar
  17. 17.
    Forster S, Triffitt JT, Bauer HC, Brosjo O, Nilsson OS, Smith R, Sykes B. Interferon-inhibited human osteosarcoma xenografts induce host bone in nude mice. J Bone Miner Res 1988; 3 (2): 199–202.PubMedGoogle Scholar
  18. 18.
    Sidky YA, Borden EC. Inhibition of angiogenesis by IFNs: effects on tumor and lymphocyte-induced vascular responses. Cancer Res 1987; 47: 5155–5161.PubMedGoogle Scholar
  19. 19.
    Gresser I. Antitumor effects of interferon. Acta Oncol 1989; 28(3): 347–53.PubMedGoogle Scholar
  20. 20.
    Gresser I. How does interferon inhibit tumor growth? Interferon 1985; 6: 93–126.PubMedGoogle Scholar
  21. 21.
    Balkwill FR. Interferons. Lancet, 1989, pp. 1060–1063.Google Scholar
  22. 22.
    Dvorak HF, Gresser I. Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. JNCI 1989; 81: 497–502.PubMedGoogle Scholar
  23. 23.
    Gresser I, Maury C, Carnaud C, De Maeyher E, Maunoury MT, Belardelli F. Anti-tumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant friend erythroleukemia cells. VIII. Role of the immune system in the inhibition of visceral metastases. Int J Cancer 1990; 46: 468–474.PubMedGoogle Scholar
  24. 24.
    Kaido T, Gresser I, Maury C, Maunoury M-T, Vignaux F, Belardelli F. Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN a/b therapy of friend erythroleukemia visceral metastases. Int J Cancer 1993; 54: 475–481.PubMedGoogle Scholar
  25. 25.
    Yasui H, Proietti E, Vignaux F, Eid P, Gresser I. Inhibition of mouse a/b-interferon of the multiplication of a/b-interferonresistant friend erythroleukemia cells cocultured with mouse hepatocytes. Cancer Res 1990; 50 (June 15): 3533–3539.PubMedGoogle Scholar
  26. 26.
    Gresser I, Kaido T, Maury C, Woodrow D, Moss J, Belardelli F. Interaction of IFNα/β with host cells essential to the early inhibition of friend erythroleukemia visceral metastases in mice. Int J Cancer 1994; 57: 604–611.PubMedGoogle Scholar
  27. 27.
    Ramani P, Hart IR, Balkwill FR. The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice. Int J Cancer 1986; 37: 563–568.PubMedGoogle Scholar
  28. 28.
    Ramani P, Balkwill FR. Action of recombinant alpha interferon against experimental and spontaneous metastases in a murine model. Int J Cancer 1989; 43: 140–146.PubMedGoogle Scholar
  29. 29.
    Kase S, Kubota T, Watanabe M, Teramoto T, Kitajima M, Hoffman RM. Recombinant human interferon alpha-2a increases 5-fluorouracil efficacy by elevating fluorouridine concentration in tumor tissue. Anticancer Res 1994; 14(3a): 1155–9.PubMedGoogle Scholar
  30. 30.
    Balkwill FR, Lee A, Aldam G, Moodie E, Thomas A, Tavernier J, Fiers W. Human tumour xenografts treated with recombinant human tumor necrosis factor alone or in combination with interferons. Cancer Res 1986; 46: 3990–3993.PubMedGoogle Scholar
  31. 31.
    Bassukas ID, Hofmockel G, Maurer Schultze B. Treatment with tumor necrosis factor alpha and interferon alpha of a human kidney cancer xenograft in nude mice: evidence for an anticachectic effect of interferon alpha. Anticancer Res 1994; 14(1a): 237–45.PubMedGoogle Scholar
  32. 32.
    Sayers TJ, Wiltrout TA, McCormick K, Husted C, Wiltrout RH. Antitumor effects of alpha-interferon and gammainterferon on a murine renal cancer (renca)in vitro andin vivo 1. Cancer Res 1990; 50: 5414–5420.PubMedGoogle Scholar
  33. 33.
    Parangi S, O'Reilly MO, Holmgrem L, Folkman J, Hanahan D. Treatment of transgenic mice with a regimen of angiogenesis inhibitors impairs tumour development. Proc. Am.Assoc. Can. Res. 1995; 36: 104.Google Scholar
  34. 34.
    Tani K. [Implantation of genetically manipulated fibroblasts into mice as a model of gene therapy-supplementations of human granulocyte colony-stimulating factor (hG-CSF) and interferon-alpha (IFN-alpha)]. Human Cell 1991; 4(1): 25–32.PubMedGoogle Scholar
  35. 35.
    Ferrantini M, Giovarelli M, Modesti A, Musiani P, Modica A, Venditti M, Peretti E, Lollini PL, Nanni P, Forni G et al. IFN-alpha 1 gene expression into a metastatic murine adenocarcinoma (TS/A) results in CD8+ T cell-mediated tumor rejection and development of antitumor immunity. Comparative studies with IFN-gamma-producing TS/A cells. J Immunol 1994; 153(10): 4604–15.PubMedGoogle Scholar
  36. 36.
    Ferrantini M, Proietti E, Santodonato L, Gabriele L, Peretti M, Plavec I, Meyer F, Kaido T, Gresser I, Belardelli F. A1-interferon gene transfer into metastatic Friend leukemia cells abrogated tumorigenicity in immunocompetent mice: antitumor therapy by means of interferon-producing cells. Cancer Res 1993; 53: 1107–1112.PubMedGoogle Scholar
  37. 37.
    Ozello L, Habif DV, De Rosa CM. Antiproliferative effects of natural IFN-beta alone and in combination with natural IFN-gamma on human breast carcinomas in nude mice. Breast Can Res Treat 1990; 16: 89–96.Google Scholar
  38. 38.
    Kase S, Kubota T, Watanabe M, Furukawa T, Tanino H, Ishibiki K, Teramoto T, Kitajima M: Interferon beta increases antitumor activity of 5-fluorouracil against human colon carcinoma cellsin vitro andin vivo. Anticancer Res 1993; 13(2): 369–73.PubMedGoogle Scholar
  39. 39.
    Johns TG, Mackay IR, Callister KA, Hertzog PJ, Devenish RJ, Linnane AW. Antiproliferative potencies of interferons on melanoma cell lines and xenografts: higher efficacy of interferon beta. J Natl Cancer Inst 1992; 84(15): 1185–90.PubMedGoogle Scholar
  40. 40.
    Tanaka N, Nagao S, Tohgo A, Sekiguchi F, Kohno M, Ogawa H, Matsui T, Matsutani M. Effects of human fibroblast interferon on human gliomas transplanted into nude mice. Gann 1983; 74: 308–316.PubMedGoogle Scholar
  41. 41.
    Nakamura O, Nomura K, Maruo K, Ueyama Y, Matsutani M, Takakura K. [Antineoplastic effect of beta-IFN and gamma-IFN on malignant gliomas]. No To Shinkei 1987; 39(7): 627–32.PubMedGoogle Scholar
  42. 42.
    Balkwill FR, Stevens MH, Griffin DB, Thomas JA, Bodmer JG. Interferon gamma regulates HLA-d expression on solid tumorsin vivo. Eur J Cancer Clin Oncol 1987; 23: 101–106.PubMedGoogle Scholar
  43. 43.
    Balkwill FR, Ward BG, Moodie E, Fiers W: Therapeutic potential of tumor necrosis factor alpha and gamma interferon in experimental human ovarian cancer. Cancer Res 1987; 47: 4755–4758.PubMedGoogle Scholar
  44. 44.
    Malik STA, Knowles RG, East N, Lando D, Stamp G, Balkwill FR. Antitumour activity of gamma interferon in ascitic and solid tumour models of human ovarian cancer. Cancer Research 1991; 51: 6643–9.PubMedGoogle Scholar
  45. 45.
    Balkwill FR, Proietti E. Effects of mouse interferon on human tumour xenografts in the nude mouse host. Int J Cancer 1986; 38: 375–380.PubMedGoogle Scholar
  46. 46.
    Ramani P, Balkwill FR. Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice. Br J Cancer 1988; 58: 350–354.PubMedGoogle Scholar
  47. 47.
    Giovarelli M, Cofano F, Vecchi A, Forni M, Landolfo S, Forni G. Interferon-activated tumor inhibition in vivo. Small amounts of interferon-gamma inhibit tumor growth by eliciting host systemic immunoreactivity. Int J Cancer 1986; 37(1): 141–8.PubMedGoogle Scholar
  48. 48.
    Kondo H, Tanaka N, Naomoto Y, Orita K. Antitumor effect of recombinant human interferon-beta and interferon-gamma in combination against human colon cancer cell line in vitro and in nude mice. Jpn J Cancer Res 1987; 78(11): 1258–65.PubMedGoogle Scholar
  49. 49.
    Ramani P, Balkwill FR. Enhanced metastases of a mouse carcinoma afterin vitro treatment with murine interferon gamma. Int J Cancer 1987; 40: 830–834.PubMedGoogle Scholar
  50. 50.
    Watanabe Y, Kuribayashi K, Miyatake S, Nishihara K, Nakayama E, Taniyama T, Sakata T. Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. Proc Natl Acad Sci USA 1989; 86(23): 9456–60.PubMedGoogle Scholar
  51. 51.
    Porgador A, Bannerji R, Watanabe Y, Feldman M, Gilboa E, Eisenbach L. Antimetastatic vaccination of tumor-bearing mice with two types of IFN-gamma gene-inserted tumor cells. J Immunol 1993; 150(4): 1458–70.PubMedGoogle Scholar
  52. 52.
    Restifo NP, Spiess PJ, Karp SE, Mule JJ, Rosenberg SA. A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability. J Exp Med 1992; 175(6): 1423–31.PubMedGoogle Scholar
  53. 53.
    Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Gilboa E. Retroviral vector-mediated g-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 1990; 50(December): 7820–7825.PubMedGoogle Scholar
  54. 54.
    Esumi N, Hunt B, Itaya T, Frost P: Reduced tumorigenicity of murine tumor cells secreting gamma-interferon is due to nonspecific host responses and is unrelated to class I major histocompatibility complex expression. Cancer Res 1991; 51(4): 1185–9.PubMedGoogle Scholar
  55. 55.
    Hiura M, Hashimura T, Watanabe Y, Kuribayashi K, Yoshida O. Induction of specific anti-tumour immunity by interferongamma gene-transferred murine bladder carcinoma MBT-2. Folia Biol Praha 1994; 40(1–2): 49–61.PubMedGoogle Scholar
  56. 56.
    Helson L, Helson C, Green S. Effects of murine tumor necrosis factor on heterotransplanted human tumors. Exp Cell Biol 1979; 47(1): 53–60.PubMedGoogle Scholar
  57. 57.
    Haranaka K, Satomi N, Sakurai A. Antitumor activity of murine tumor necrosis factor (TNF) Against transplanted murine tumors and heterotransplanted human tumors in nude mice. Int J Cancer 1984; 34: 263–267.PubMedGoogle Scholar
  58. 58.
    Creasey AA, Reynolds MT, Laird W. Cures and partial regression of murine and human tumors by recombinant human tumor necrosis factor. Cancer Res 1986; 46(November): 5687–5690.PubMedGoogle Scholar
  59. 59.
    Nosoh Y, Toge T, Nishiyama M, Yamaguchi M, Hirabayashi N, Niimoto M, Hattori T. Antitumor effects of recombinant human tumor necrosis factor against human tumor xenografts transplanted into nude mice. Jpn J Surg 1987; 17(1): 51–54.PubMedGoogle Scholar
  60. 60.
    Sohmura Y, Nakata K, Yoshida H, Kashimoto S, Matsui Y, Furuichi H. Recombinant human tumor necrosis factor-II. Antitumor effect on murine and human tumors transplanted in mice. Int J Immunopharmacol 1986; 8(3): 357–68.PubMedGoogle Scholar
  61. 61.
    Manetta A, Podczaski E, Zaino RJ, Satyaswaroop PG. Therapeutic effect of recombinant human tumor necrosis factor in ovarian carcinoma xenograft in nude mice. Gynecol Oncol 1989; 34(3): 360–4.PubMedGoogle Scholar
  62. 62.
    Malik STAA, Griffin DB, Fiers W, Balkwill FR: Paradoxical effects of tumour necrosis factor in experimental ovarian cancer. Int J Cancer 1989; 44: 918–925.PubMedGoogle Scholar
  63. 63.
    Malik S: The activity of TNF in experimental cancer models. In: Beutler B ed, Tumor Necrosis Factors. Dallas, Texas, Raven Press New York, 1992.Google Scholar
  64. 64.
    Carswell EA, Old LJ, Kassel RJ, Green S, Fiore N, Williamson B: An endotoxin-induced serum factor that causes necrosis of tumours. Proc Natl Acad Sci USA 1975; 72: 3666–3670.PubMedGoogle Scholar
  65. 65.
    Manda T, Shimomura K, Mukumoto S, Kobayashi K, Mizota T, Hirai O, Matsumoto S, Oku T, Nishigaki F, Mori J, Kikuchi H. Recombinant human tumor necrosis factor alpha: evidence of an indirect mode of antitumor activity. Cancer Res 1987; 47: 3707–3711.PubMedGoogle Scholar
  66. 66.
    Mule JJ, Asher A, McIntosh J, Lafreniere R, Shiloni E, Lefor A, Reichert CM, Rosenberg SA. Antitumor effect of recombinant tumor necrosis factor-alpha against murine sarcomas at visceral sites: tumor size influences the response to therapy. Cancer Immunol Immunother 1988; 26(3): 202–8.PubMedGoogle Scholar
  67. 67.
    Tomazic VJ, Farha M, Loftus A, Elias EG. Anti-tumor activity of recombinant tumor necrosis factor on mouse fibrosarcoma in vivo and in vitro. J Immunol 1988; 140(11): 4056–61.PubMedGoogle Scholar
  68. 68.
    Palladino MA, Jr., Shalaby MR, Kramer SM, Ferraiolo BL, Baughman RA, Deleo AB, Crase D, Marafino B, Aggarwal BB, Figari IS,et al. Characterization of the antitumor activities of human tumor necrosis factor-alpha and the comparison with other cytokines: induction of tumor-specific immunity. J Immunol 1987; 138(11): 4023–32.PubMedGoogle Scholar
  69. 69.
    Havell EA, Fiers W, North RJ. The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med 1988; 167(3): 1067–85.PubMedGoogle Scholar
  70. 70.
    al Attiyah R, Rosen H, Rook GA. A model for the investigation of factors influencing haemorrhagic necrosis mediated by tumour necrosis factor in tissue sites primed with mycobacterial antigen preparations. Clin Exp Immunol 1992; 88(3): 537–42.PubMedGoogle Scholar
  71. 71.
    Malik STA, Naylor S, East N, Oliff A, Balkwill FR. Cells secreting tumour necrosis factor show enhanced metastasis in nude mice. Eur J Cancer 1990; 26(10): 1031–1034.PubMedGoogle Scholar
  72. 72.
    Nishiyama Y, Fuchimoto S, Orita K. Preventive and antiproliferative effects of tumor necrosis factor against experimental hepatic metastases of mouse colon-26 tumor. Jpn J Cancer Res 1989; 80(4): 366–72.PubMedGoogle Scholar
  73. 73.
    Orosz P, Echtenacher B, Falk W, Ruschoff J, Weber D, Mannel DN. Enhancement of experimental metastasis by tumor necrosis factor. J Exp Med 1993; 177(5): 1391–8.PubMedGoogle Scholar
  74. 74.
    Talmadge JE, Tribble HR, Pennington RW, Phillips H, Wiltrout RH. Immunomodulatory and immunotherapeutic properties of recombinant gamma interferon and recombinant tumor necrosis factor in mice. Cancer Res 1987; 47: 2563–2570.PubMedGoogle Scholar
  75. 75.
    Baisch H, Otto U, Kloppel G. Antiproliferative and cytotoxic effects of single and combined treatment with tumor necrosis factor alpha and/or alpha interferon on a human renal cell carcinoma xenotransplanted into nu/nu mice: cell kinetic studies. Cancer Res 1990; 50(19): 6389–95.PubMedGoogle Scholar
  76. 76.
    Winkelhake JL, Stampfl S, Zimmerman RJ. Synergistic effects of combination therapy with human recombinant interleukin-2 and tumor necrosis factor in murine tumor models. Cancer Res 1987; 47(15): 3948–53.PubMedGoogle Scholar
  77. 77.
    McIntosh JK, Mule JJ, Krosnick JA, Rosenberg SA. Combination cytokine immunotherapy with tumor necrosis factor alpha, interleukin 2 and alpha-interferon and its synergistic antitumor effects in mice. Cancer Res 1989; 49: 1408–1414.PubMedGoogle Scholar
  78. 78.
    Ohkura M, Fuchimoto S, Orita K. Antitumor effect of recombinant human interleukin-1β alone and in combination with natural human tumor necrosis factor-α. Jpn J Cancer Res 1990; 81(October): 1026–1031.PubMedGoogle Scholar
  79. 79.
    Mule JJ, McIntosh JK, Jablons DM, Rosenberg SA. Antitumor activity of recombinant interleukin 6 in mice. J Exp Med 1990;171: 629–636.PubMedGoogle Scholar
  80. 80.
    de Kossodo S, Moore R, Gschmeissner S, East N, Upton C, Balkwill F. Changes in endogenous cytokines, adhesion molecules and platelets during cytokine induced tumour necrosis. Brit. J. Can. 1995; in press.Google Scholar
  81. 81.
    Oliff A, Defeo Jones D, Boyer M, Martinez D, Kiefer D, Vuocolo G, Wolfe A, Socher SH. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell 1987; 50(4): 555–63.PubMedGoogle Scholar
  82. 82.
    Blankenstein T, Qin ZH, Uberla K, Muller W, Rosen H, Volk HD, Diamantstein T. Tumor suppression after tumor celltargeted tumor necrosis factor alpha gene transfer. J Exp Med 1991; 173(5): 1047–52.PubMedGoogle Scholar
  83. 83.
    Teng MN, Park BH, Koeppen HK, Tracey KJ, Fendly BM, Schreiber H. Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity. Proc Natl Acad Sci USA 1991; 88(9): 3535–9.PubMedGoogle Scholar
  84. 84.
    Asher AL, Mule JJ, Kasid A, Restifo NP, Salo JC, Reichert CM, Jaffe G, Fendly B, Kriegler M, Rosenberg SA. Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors. J Immunol 1991; 146(9): 3227–34.PubMedGoogle Scholar
  85. 85.
    Yannelli JR, Hyatt C, Johnson S, Hwu P, Rosenberg SA. Characterization of human tumor cell lines transduced with the cDNA encoding either tumor necrosis factor alpha (TNF-a) or interleukin-2 (IL-2). J Immunol Methods 1993; 161(1): 77–90.PubMedGoogle Scholar
  86. 86.
    Mizuno M, Yoshida J, Oyama H, Sugita K. Growth inhibition of glioma cells by liposome-mediated cell transfection with tumor necrosis factor-alpha gene-its enhancement by prior gamma-interferon treatment. Neurol Med Chir Tokyo 1992; 32(12): 873–6.PubMedGoogle Scholar
  87. 87.
    Marincola FM, Venzon D, White D, Rubin JT, Lotze MT, Simonis TB, Balkissoon J, Rosenberg SA, Parkinson DR. HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. Cancer Res 1992; 52: 6561–6566.PubMedGoogle Scholar
  88. 88.
    Moore AS, Theilen GH, Newell AD, Madewell BR, Rudolf AF. Preclinical study of sequential tumor necrosis factor and interleukin 2 in the treatment of spontaneous canine neoplasms. Cancer Res 1991; 51(Jan. 1): 233–238.PubMedGoogle Scholar
  89. 89.
    Papa MZ, Vetto JT, Ettinghausen SE, Mule JJ, Rosenberg SA. Effect of corticosteroid on the antitumor activity of lymphokine-activated killer cells and interleukin 2 in mice. Cancer Res 1986; 46: 5618–5623.PubMedGoogle Scholar
  90. 90.
    Ettinghausen SE, Rosenberg SA. Immunotherapy of murine sarcomas using lymphokine activated killer cells: optimization of the schedule and route of administration of recombinant interleukin-2. Cancer Res 1986; 46: 2784–92.PubMedGoogle Scholar
  91. 91.
    Paciotti GF, Tamarkin L: Interleukin-2 differentially affects the proliferation of a hormone-dependent and a hormoneindependent human breast cancer cell linein vitro andin vivo. Anticancer Res 1988; 8(6): 1233–9.PubMedGoogle Scholar
  92. 92.
    Sacchi M, Vitolo D, Sedlmayr P, Rabinowich H, Johnson JT, Herberman RB, Whiteside TL. Induction of tumor regression in experimental model of human head and neck cancer by human A-LAK cells and IL-2. Int J Cancer 1991; 47(5): 784–91.PubMedGoogle Scholar
  93. 93.
    Sacchi M, Snyderman CH, Heo DS, Johnson JT, d'Amico F, Herberman RB, Whiteside TL. Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine-activated killer cells and interleukin 2. Cancer Res 1990; 50(10): 3113–8.PubMedGoogle Scholar
  94. 94.
    Weidmann E, Sacchi M, Plaisance S, Heo DS, Yasumura S, Lin WC, Johnson JT, Herberman RB, Azzarone B, Whiteside TL. Receptors for interleukin 2 on human squamous cell carcinoma cell lines and tumor in situ. Cancer Res 1992; 52(21): 5963–70.PubMedGoogle Scholar
  95. 95.
    Rabinowich H, Vitolo D, Altarac S, Herberman RB, Whiteside TL. Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2-activated natural killer cells. J Immunol 1992; 149(1): 340–9.PubMedGoogle Scholar
  96. 96.
    Vujanovic NL, Yasumura S, Hirabayashi H, Lin WC, Watkins S, Herberman RB, Whiteside TL. Antitumor activities of subsets of human IL-2-activated natural killer cells in solid tissues. J Immunol 1995; 154(1): 281–9.PubMedGoogle Scholar
  97. 97.
    Greenberg PD. Therapy of murine leukemia with cyclophosphamide and immune Lyt-2+ cells: cytolytic T cells can mediate eradication of disseminated leukemia. J Immunol 1986; 136(5): 1917–22.PubMedGoogle Scholar
  98. 98.
    Mule JJ, Smith CA, Rosenberg SA. Interleukin 4 can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells. J Exp Med 1987; 166: 792–797.PubMedGoogle Scholar
  99. 99.
    Talmadge JE, Phillips H, Schindler J, Tribble H, Pennington R. Systematic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease. Cancer Res 1987; 47: 5725–5732.PubMedGoogle Scholar
  100. 100.
    Foa R, Fierro MT, Raspadori D, Bonferroni M, Cardona S, Guarini A, Tos AG, Di Celle F, Cesano A, Matera L, Lauria F, Gavosto F. Lymphokine-activated killer (LAK) cell activity in B and Tchronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous lak effectors. Blood 1990; 76(7): 1349–1354.PubMedGoogle Scholar
  101. 101.
    Herberman RB, Nunn ME, Lavrin DH. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 1975; 16(2): 216–29.PubMedGoogle Scholar
  102. 102.
    Lafreniere R, Rosenberg SA. Adoptive immunotherapy of murine hepatic metastases with lymphokine activaed killer (LAK) cells and recombinant interleukin 2 (RIL)2. J Immunol 1985; 135: 4273–4280.PubMedGoogle Scholar
  103. 103.
    Mule JJ, Shu S, Rosenber SA. The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2in vivo. J Immunol 1985; 135: 642–646.PubMedGoogle Scholar
  104. 104.
    Rosenberg SA, Mule JJ, Spiess J, Reichert CM, Schwarz SL. Regression of established pulmonary metastases and subcutaneous tumor mediated by systemic administration of highdose recombinant interleukin. J Exp Med 1985; 161: 1169–1188.PubMedGoogle Scholar
  105. 105.
    Hirabayashi H, Yasumura S, Lin WC, Amoscato A, Johnson JT, Herberman RB, Whiteside TL. Production by human squamous cell carcinoma of a factor inducing activation and proliferation of immune cells. Arch Otolaryngol Head Neck Surg 1995; 121(3): 285–92.PubMedGoogle Scholar
  106. 106.
    Henney CS, Kuribayashi K, Kern DE, Gillis S. Interleukin-2 augments natural killer cell activity. Nature 1981; 291(5813): 335–8.PubMedGoogle Scholar
  107. 107.
    Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 1986; 233: 1318–21.PubMedGoogle Scholar
  108. 108.
    Schwarz RE, Vujanovic NL, Hiserodt JC. Enhanced antimetastatic activity of lymphokine-activated killer cells purified and expanded by their adherence to plastic. Cancer Res 1989; 49(6): 1441–6.PubMedGoogle Scholar
  109. 109.
    Mule JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 1984; 225(4669): 1487–9.PubMedGoogle Scholar
  110. 110.
    Ettinghausen SE, Rosenberg SA. The adoptive immunotherapy of cnancer using lymphokine activated killer cells and recombinant interleukin-2. Springer Semin Immunopathol 1986; 9: 51–71.PubMedGoogle Scholar
  111. 111.
    Brunda MJ. Antitumour activity of interleukin-2 combined with other cytokines. In. Waxman JABFR ed: Interleukin-2. London, Blackwell Scientific Publications, 1992, p 106–121.Google Scholar
  112. 112.
    Brunda MJ, Bellantoni D, Sulich V.In vivo anti-tumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cytotoxic cells resembling natural killer cells. Int J Cancer 1987; 40: 365–371.PubMedGoogle Scholar
  113. 113.
    Iigo M, Sakurai M, Tamura T, Saijo N, Hoshi A.In vivo antitumor activity of multiple injections of recombinant interleukin 2, alone and in combination with three different types of recombinant interferon, on various syngeneic murine tumors. Cancer Res 1988; 48(2): 260–4.PubMedGoogle Scholar
  114. 114.
    Truitt GA, Brunda MJ, Levitt D, Anderson TD, Sherman MI. The therapeutic activity in cancer of IL-2 in combination with other cytokines. Cancer Surv 1989; 8(4): 875–89.PubMedGoogle Scholar
  115. 115.
    Sakura Y, Ootsu K, Shino A. Combination therapy of colon carcinoma 26 in mice with recombinant human interleukin-2 and interferon-alpha A/D: occurrence of large granular cells in the tumor. Jpn J Cancer Res 1989; 80(9): 895–903.PubMedGoogle Scholar
  116. 116.
    Kim B, Stein S, Warnaka P, Franceschi D. Enhanced in vivo therapy of pulmonary metastases with interferon and interleukin-2. J Surg Res 1988: 45(1): 66–73.PubMedGoogle Scholar
  117. 117.
    Rosenberg SA, Schwarz SL, Spiess PJ. Combination immunotherapy for cancer: synergistic antitumor interactions of interleukin-2 alfa interferon, and tumor-infiltrating lymphocytes. JNCI 1988; 80: 1393–1397.PubMedGoogle Scholar
  118. 118.
    Hornung RL, Back TC, Zaharko DS, Urba WJ, Longo DL, Wiltrout RH. Augmentation of natural killer activity, induction of IFN and development tumor immunity during the successful treatment of established murine renal cancer using flavone acetic acid and IL-2. J Immunol 1988; 141(10): 3671–9.PubMedGoogle Scholar
  119. 119.
    Cameron RB, McIntosh JK, Rosenberg SA. Synergistic antitumor effects of combination immunotherapy with recombinant interleukin-2 and a recombinant hybrid alpha interferon in the treatment of established murien hepatic metastases. Cancer Res 1988; 48: 5810–5817.PubMedGoogle Scholar
  120. 120.
    Silagi S, Dutkowski R, Schaefer A. Eradication of mouse melanoma by combined treatment with recombinant human interleukin 2 and recombinant murine interferon-gamma. Int J Cancer 1988; 41(2): 315–22.PubMedGoogle Scholar
  121. 121.
    Agah R, Malloy B, Sherrod A, Mazumder A. Successful therapy of natural killer-resistant pulmonary metastases by the synergism of gamma-interferon with tumor necrosis factor and interleukin-2 in mice. Cancer Res 1988; 48(8): 2245–8.PubMedGoogle Scholar
  122. 122.
    Dubinett SM, Kurnick JT, Kradin RL. Adoptive immunotherapy of murine pulmonary metastases with interleukin 2 and interferon-gamma. Am J Respir Cell Mol Biol 1989; 1(5): 361–9.PubMedGoogle Scholar
  123. 123.
    Nishimura T, Ohta S, Sato N, Togashi Y, Goto M, Hashimoto Y. Combination tumor-immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice. Int J Cancer 1987; 40(2): 255–61.PubMedGoogle Scholar
  124. 124.
    Ward BG, Wallace K, Shepherd JH, Balkwill FR. Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice. Cancer Res 1987; 47: 2662–2667.PubMedGoogle Scholar
  125. 125.
    Mahadevan V, Malik ST, Meager A, Fiers W, Lewis GP, Hart IR. Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown. Cancer Res 1990; 50(17): 5537–412.PubMedGoogle Scholar
  126. 126.
    McIntosh JK, Mule JJ, Merino MJ, Rosenberg SA. Synergistic antitumor effects of immunotherapy with recombinant interleukin-2 and recombinant tumor necrosis factor alpha. Cancer Res 1988; 48: 4011–4017.PubMedGoogle Scholar
  127. 127.
    Iigo M, Nishikata K, Hoshi A. Effect of recombinant interleukin-1 alpha, recombinant interleukin-2, recombinant interferon-beta, and recombinant tumor necrosis factor on subcutaneously implanted adenocarcinoma 755 and Lewis lung carcinoma. J Biol Response Mod 1990; 9(4): 426–30.PubMedGoogle Scholar
  128. 128.
    Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172(October): 1217–1224, 1990.PubMedGoogle Scholar
  129. 129.
    Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 1990; 60(3): 397–403.PubMedGoogle Scholar
  130. 130.
    Gansbacher B, Zier K, Cronin K, Hantzopoulos PA, Bouchard B, Houghton A, Gilboa E, Golde D. Retroviral gene transfer induced constitutive expression of interleukin-2 or interferongamma in irradiated human melanoma cells. Blood 1992; 80(11): 2817–25.PubMedGoogle Scholar
  131. 131.
    Bubenik J, Simova J, Jandlova T. Immunotherapy of cancer using local administration of lymphoid cells transformed by IL-2 cDNA and constitutively producing IL-2. Immunol Lett 1990; 23(4): 287–92.PubMedGoogle Scholar
  132. 132.
    Ley V, Langlade Demoyen P, Kourilsky P, Larsson Sciard EL. Interleukin 2-dependent activation of tumor-specific cytotoxic T lymphocytes in vivo. Eur J Immunol 1991; 21(3): 851–4.PubMedGoogle Scholar
  133. 133.
    Russell SJ, Eccles SA, Flemming CL, Johnson CA, Collins MK. Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL-2 cDNA. Int J Cancer 1991; 47(2): 244–51.PubMedGoogle Scholar
  134. 134.
    Connor J, Bannerji R, Saito S, Heston W, Fair W, Gilboa E. Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells [published erratum appears in J Exp Med 1993 Jun 1; 177(6): following 1831]. J Exp Med 1993; 177(4): 1127–34.PubMedGoogle Scholar
  135. 135.
    Foa R, Guarini A, Cignetti A, Cronin K, Rosenthal F, Gansbacher B. Cytokine gene therapy: a new strategy for the management of cancer patients. Nat Immun 1994; 13(2–3): 65–75.PubMedGoogle Scholar
  136. 136.
    Fearon ER, Pardoll DM, Iaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P. Interleukin-2 production by tumor cells bypasses t helper function in the generation of an antitumor response. Cell 1990; 60: 397–403.PubMedGoogle Scholar
  137. 137.
    Abdel Wahab Z, Li WP, Osanto S, Darrow TL, Hessling J, Vervaert CE, Burrascano M, Barber J, Seigler HF. Transduction of human melanoma cells with interleukin-2 gene reduces tumorigenicity and enhances host antitumor immunity: a nude mouse model. Cell Immunol 1994; 159(1): 26–39.PubMedGoogle Scholar
  138. 138.
    Miller AR, McBride WH, Dubinett SM, Dougherty GJ, Thacker JD, Shau H, Kohn DB, Moen RC, Walker MJ, Chiu R,et al. Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: comparison of immunologic properties with interleukin-2. Blood 1993; 82(12): 3686–94.PubMedGoogle Scholar
  139. 139.
    Karp SE, Farber A, Salo JC, Hwu P, Jaffe G, Asher AL, Shiloni E, Restifo NP, Mule JJ, Rosenberg SA. Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma. Tumor inhibition by IL-2 but not tumor necrosis factor. J Immunol 1993; 150(3): 896–908.PubMedGoogle Scholar
  140. 140.
    Cavallo F, Giovarelli M, Gulino A, Vacca A, Stoppacciaro A, Modesti A, Forni G. Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene. J Immunol 1992; 149(11): 3627–35.PubMedGoogle Scholar
  141. 141.
    Bubenik J, Simova J, Bubenikova D, Zeuthen J, Indrova M. Interleukin-2 gene therapy of residual EL-4 leukaemia potentiates the effect of cyclophosphamide pretreatment. J Cancer Res Clin Oncol 1992; 121(1): 39–43.Google Scholar
  142. 142.
    Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J exp med 1993; 178(October): 1223–1230.PubMedGoogle Scholar
  143. 143.
    Nastala CL, Edington HD, McKinney TG, Tahara H, Nalesnik MA, Brunda MJ, Gately MK, Wolf SF, Schreiber RD, Storkus WJ,et al. Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. J Immunol 1994; 153(4): 1697–706.PubMedGoogle Scholar
  144. 144.
    Gately MK, Gubler U, Brunda MJ, Nadeau Rr, Anderson TD, Lipman JM, Sarmiento U. Interleukin-12: a cytokine with therapeutic potential in oncology and infectious diseases. Therapeutic Immunol In press, 1994.Google Scholar
  145. 145.
    O'Toole M, Wolf S, O'Brien C, Hubbard B, Herrmann S. Effect ofin vivo IL-12 administration on murine tumour cell growth. J Immunol 1993; 150: 294A.Google Scholar
  146. 146.
    Tahara H, Zeh HJr, Storkus WJ, Pappo I, Watkins SC, Gubler U, Wolf SF, Robbins PD, Lotze MT. Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo. Cancer Res 1994; 54(1): 182–9.PubMedGoogle Scholar
  147. 147.
    Pappo I, Tahara H, Robbins PD, Gately MK, Wolf SF, Barnea A, Lotze MT. Administration of systemic or local interleukin2 enhances the anti-tumor effects of interleukin-12 gene therapy. J Surg Res 1995; 58(2): 218–26.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Frances Burke
    • 1
  • Frances R. Balkwill
    • 1
  1. 1.Biological Therapies LaboratoryImperial Cancer Research FundLondonUK

Personalised recommendations