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Cytokine-mediated gene therapy for cancer

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Abstract

Background: Significant interest has been generated in the gene therapy of cancer. One strategy involves tumor-directed cytokine gene transfer and its effects on tumor immunobiology.

Methods: The authors review the current literature pertaining to cytokine gene therapy of cancer and provide a description of gene transfer methods currently being evaluated.

Results: Several cytokine gene transfer models have been described involving at least 12 different cytokines. The introduction of cytokine genes into experimental animal tumors improves their ability to be recognized and destroyed by the host immune system. Certain cytokines will regulate phenotypic properties such as major histocompatibility complex antigens, immunosuppressive peptides, protooncogenes or endogenous cytokine production. Cytokine-transduced tumors attract an inflammatory exudate in vivo that generally results in tumor destruction. The nature of the infiltrate (lymphocytic, mononuclear, granulocytic) cannot always be predicted from the known biological properties of each cytokine. Untransduced bystander tumor cells are usually also destroyed. Some, but not all, cytokine transductions result in the generation of systemic major histocompatibility complex-restricted, tumor immunity. It has been hypothesized that the local continuous production of cytokines by tumor cells provides an optimal microenvironment for antigen recognition and the generation of T-cell immunity.

Conclusions: These experimental observations hold promise for the clinical application of genetically engineered tumor vaccines.

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References

  1. Wheelock EF. An overview of mechanisms responsible for tumor dormancy. In: Stewart THM, Wheelock EF, eds.Cellular immune mechanisms and tumor dormancy. Boca Raton, FL: CRC Press, 1992:1–13.

    Google Scholar 

  2. Bast RC Jr. Principles of cancer biology: tumor immunology. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.Cancer principles and practice of oncology. Philadelphia, PA: JB Lippincott, 1985:125–50.

    Google Scholar 

  3. Rosenberg SA, Lotze MT, Yang JC, et al. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients.Ann Surg 1989;210:474–84.

    CAS  PubMed  Google Scholar 

  4. 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;67:1067–85.

    Google Scholar 

  5. Colombo MP, Modesti A, Parmiani G, Forni G. Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T-lymphocyte cross-talk.Cancer Res 1992;52:4853–7.

    CAS  PubMed  Google Scholar 

  6. Uchiyama A, Hoon DSB, Morisaki T, Kaneda Y, Yuzuki DH, Morton DL. Transfection of interleukin 2 gene into human melanoma cells augments cellular immune response.Cancer Res 1993;53:949–52.

    CAS  PubMed  Google Scholar 

  7. Belldegrun A, Tso CL, Sakata T, et al. Human renal carcinoma line transfected with interleukin-2 and/or interferon-a gene(s): implications for live cancer vaccines.J Natl Cancer Inst 1993;85:207–16.

    CAS  PubMed  Google Scholar 

  8. Torre-Amione G, Beauchamp RD, Koeppen H, et al. A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune surveillance.Proc Natl Acad Sci USA 1990;87:1486–90.

    CAS  PubMed  Google Scholar 

  9. Karp SE, Farber A, Salo JC, et al. Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma.J Immunol 1993;150:896–908.

    CAS  PubMed  Google Scholar 

  10. Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine ganulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.Proc Natl Acad Sci USA 1993;90:3539–43.

    CAS  PubMed  Google Scholar 

  11. Hock H, Dorsch M, Kunzendorf U, et al. Vaccinations with tumor cells genetically engineered to produce different cytokines: effectivity not superior to a classical adjuvant.Cancer Res 1993;53:714–6.

    CAS  PubMed  Google Scholar 

  12. Kriegler M.Gene transfer and expression. New York: Stockton Press, 1990:96–102.

    Google Scholar 

  13. Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA.Virology 1973;52:456–67.

    Article  CAS  PubMed  Google Scholar 

  14. Andreason GL, Evans GA. Introduction and expression of DNA molecules in eukaryotic cells by electroporation.Biotechniques 1988;6:650–9.

    CAS  PubMed  Google Scholar 

  15. Nabel EG, Plautz G, Nabel GJ. Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis.Proc Natl Acad Sci USA 1992;89:5157–61.

    CAS  PubMed  Google Scholar 

  16. Plautz GE, Yang Z-Y, Wu B-Y, Gao X, Huang L, Nabel GJ. Immunotherapy of malignancy by in vivo gene transfer into tumors.Proc Natl Acad Sci USA 1993;90:4645–9.

    CAS  PubMed  Google Scholar 

  17. Stewart MJ, Plautz GE, Buono LD, et al. Gene transfer in vivo with DNA-liposome complexes: safety and acute toxicity in mice.Hum Gene Ther 1992;3:267–75.

    CAS  PubMed  Google Scholar 

  18. Nabel GJ, Chang A, Nabel EG, et al. Immunotherapy of malignancy by in vivo gene transfer into tumors.Hum Gene Ther 1992;3:399–410.

    Google Scholar 

  19. McLachlin JR, Cornetta K, Eglitis MA, Anderson WF. Retroviral-mediated gene transfer.Prog Nucl Acid Res Mol Biol 1990;38:91–133.

    CAS  Google Scholar 

  20. Hesdorffer C, Markowitz D, Ward M, Bank A. Somatic gene therapy.Hematol Oncol Clin North Am 1991;5:423–33.

    CAS  PubMed  Google Scholar 

  21. Donahue RE, Kessler SW, Bodine D, et al. Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer.J Exp Med 1992;176:1125–35.

    Article  CAS  PubMed  Google Scholar 

  22. Temin HM. Retrovirus vectors: promise and reality.Science 1989;244:983.

    Google Scholar 

  23. Muzyczka N. Use of adeno-associated virus as a general transduction vector for mammalian cells.Curr Topics Microbiol Immunol 1991;158:97–129.

    Google Scholar 

  24. Berkner KL. Development of adenovirus vectors for the expression of heterologous genes.Biotechniques 1988;6:616–29.

    CAS  PubMed  Google Scholar 

  25. Graham FL, Prevec L. Adenovirus-based expression vectors and recombinant vaccines. In: Ellis RW, ed.Vaccines: new approaches to immunological problems. Oxford, England: Butterworth-Heinemann, 1991:363–90.

    Google Scholar 

  26. Smith KA. Interleukin-2: Inception, impact, and implications.Science 1988;240:1169–76.

    CAS  PubMed  Google Scholar 

  27. Staren ED, Essner R, Economou JS. Overview of biological response modifiers.Semin Surg Oncol 1989;5:379–84.

    CAS  PubMed  Google Scholar 

  28. Rosenberg SA. Immunotherapy and gene therapy of cancer.Cancer Res 1991(suppl);51:5074s-9s.

    CAS  PubMed  Google Scholar 

  29. Russell SJ, Eccles SA, Flemming CL, Johnson CA, Collins MKL. Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL-2 cDNA.Int J Cancer 1991;47:244–51.

    CAS  PubMed  Google Scholar 

  30. 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 1990;172:1217–24.

    Article  CAS  PubMed  Google Scholar 

  31. 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 1989;23:287–92.

    Google Scholar 

  32. Miller AR, McBride WH, Dubinett SM, et al. Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: comparison of immunological properties with IL-2.Blood 1993;82:3686–94.

    CAS  PubMed  Google Scholar 

  33. Gastl G, Finstad CL, Guarini A, et al. Retroviral vector-mediated lymphokine gene transfer into human renal cancer cells.Cancer Res 1992;52:6229–36.

    CAS  PubMed  Google Scholar 

  34. Gansbacher B, Zier K, Cronin K, et al. Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-γ in irradiated human melanoma cells.Blood 1992;80:2817–25.

    CAS  PubMed  Google Scholar 

  35. Fearon ER, Pardoll DM, Itaya T, et al. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response.Cell 1990;60:397–403.

    Article  CAS  PubMed  Google Scholar 

  36. Cavallo F, Giovarelli M, Gulino A, et al. 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;149:3627–35.

    CAS  PubMed  Google Scholar 

  37. Rosenberg SA. Immunization of cancer patients using autologous cancer cells modified by insertion of the gene for interleukin-2.Hum Gene Ther 1992;3:75–90.

    Google Scholar 

  38. Rosenberg SA. Immunization of cancer patients using autologous cancer cells modified by insertion of the gene for tumor necrosis factor.Hum Gene Ther 1992;3:57–73.

    Google Scholar 

  39. Howard M, Farrar J, Hilfiker M, et al. Identification of a T cell-derived B cell growth factor distinct from interleukin 2.J Exp Med 1982;155:914–23.

    Article  CAS  PubMed  Google Scholar 

  40. Widmer MB, Grabstein KH. Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor.Nature 1987;326:795–8.

    Article  CAS  PubMed  Google Scholar 

  41. Fernandez-Botran R, Sanders VM, Oliver KG, et al. Inter-leukin 4 mediates autocrine growth of helper T cells after antigenic stimulation.Proc Natl Acad Sci USA 1986;83:9689–93.

    CAS  PubMed  Google Scholar 

  42. Paul WE, Ohara J. B-cell stimulatory factor-1/Interleukin 4.Ann Rev Immunol 1987;5:429–59.

    CAS  Google Scholar 

  43. Trenn G, Takayama H, Hu-Li J, Paul WE, Sitkovsky MV. B cell stimulatory factor 1 (IL-4) enhances the development of cytotoxic T cells from Lyt-2+ resting murine T lymphocytes.J Immunol 1988;140:1101–6.

    CAS  PubMed  Google Scholar 

  44. Lee JD, Swisher SG, Minehart EH, McBride WH, Economou JS. Interleukin-4 downregulates interleukin-6 production in human peripheral blood mononuclear cells.J Leukoc Biol 1990;47:475–9.

    CAS  PubMed  Google Scholar 

  45. Essner R, Rhoades K, McBride WH, Morton DL, Economou JS. Interleukin-4 down-regulates IL-1 and TNF gene expression in human monocytes.J Immunol 1989;142:3857.

    CAS  PubMed  Google Scholar 

  46. Totpal K, Aggarwal BB. Interleukin 4 potentiates the anti-proliferative effects of tumor necrosis factor on various tumor cell lines.Cancer Res 1991;51:4266–70.

    CAS  PubMed  Google Scholar 

  47. Balkwill FR, Burke F. The cytokine network.Immunol Today 1989;10:299–304.

    Article  CAS  PubMed  Google Scholar 

  48. Kawakami Y, Rosenberg SA, Lotze MT. Interleukin 4 promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma.J Exp Med 1988;168:2183–91.

    Article  CAS  PubMed  Google Scholar 

  49. Mule JJ, Smith CA, Rosenberg SA. Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells.J Exp Med 1987;166:792–7.

    Article  CAS  PubMed  Google Scholar 

  50. Wong HL, Lotze MT, Wahl LM, Wahl SM. Administration of recombinant IL-4 to humans regulates gene expression, phenotype, and function in circulating monocytes.J Immunol 1992;148:2118–25.

    CAS  PubMed  Google Scholar 

  51. Tepper RI, Pattengale PK, Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo.Cell 1989;57:503–12.

    Article  CAS  PubMed  Google Scholar 

  52. Golumbek PT, Lazenby AJ, Levitsky HI, et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4.Science 1991;254:713–6.

    CAS  PubMed  Google Scholar 

  53. Li W, Diamanstein T, Blankenstein T. Lack of tumorigenicity of interleukin 4 autocrine growing cells seems related to the anti-tumor function of interleukin 4.Mol Immunol 1990;27:1331–7.

    CAS  PubMed  Google Scholar 

  54. Tepper RI, Coffman RL, Leder P. An eosinophil-dependent mechanism for the antitumor effect of interleukin-4.Science 1992;257:548–51.

    CAS  PubMed  Google Scholar 

  55. Pardoll D. Immunotherapy with cytokine gene-transduced tumor cells: the next wave in gene therapy for cancer.Curr Opin Oncol 1992;4,1124–9.

    CAS  PubMed  Google Scholar 

  56. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors.Proc Natl Acad Sci USA 1975;72:3666–70.

    CAS  PubMed  Google Scholar 

  57. Nedwin GE, Svedersky LP, Bringman TS, Palladino MA, Goeddel DV. Effect of interleukin 2, interferon-g, and mitogens on the production of tumor necrosis factors a and b.J Immunol 1985;135:2492–7.

    CAS  PubMed  Google Scholar 

  58. Goeddel DV, Aggarwal BB, Gray PW, et al. Tumor necrosis factors: gene structure and biological activities. In:Cold Spring Harbor symposia on quantitative biology. Vol LI. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1986:597–609.

    Google Scholar 

  59. Collins T, Lapierre LA, Fiers W, Strominger JL, Pober JS. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A, B antigens in vascular endothelial cells and dermal fibroblasta in vitro.Proc Natl Acad Sci USA 1986;83:446–50.

    CAS  PubMed  Google Scholar 

  60. Sung S-SJ, Bjorndahl JM, Wang CY, Kao HT, Fu SM. Production of tumor necrosis factor/cachectin by human T cell lines and peripheral blood T lymphocytes stimulated by phorbol myristate acetate and anti-CD3 antibody.J Exp Med 1988;167:937–53.

    Article  CAS  PubMed  Google Scholar 

  61. Sung S-SJ, Jung LKL, Walters JA, Chen W, Wang CY, Fu SM. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells.J Exp Med 1988;168:1539–51.

    Article  CAS  PubMed  Google Scholar 

  62. Locksley RM, Heinzel FP, Shepard HM, et al. Tumor necrosis factors α and β differ in their capacities to generate interleukin 1 release from human endothelial cells.J Immunol 1987;139:1891–5.

    CAS  PubMed  Google Scholar 

  63. Yokota S, Geppert TD, Lipsky PE. Enhancement of antigen-and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-a.J Immunol 1988;140:531–6.

    CAS  PubMed  Google Scholar 

  64. Tracey KJ, Vlassara H, Cerami A. Cachectin/tumor necrosis factor.Lancet 1989;1:1122–6.

    CAS  PubMed  Google Scholar 

  65. Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Palladino MA, Shepard HM. Recombinant human tumor necrosis factor-α: effects on proliferation of normal and transformed cells in vitro.Science 1985;230:943–5.

    CAS  PubMed  Google Scholar 

  66. Urban JL, Shepard HM, Rothstein JL, Sugarman BJ, Schreiber H. Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages.Proc Natl Acad Sci USA 1986;83:5233–7.

    CAS  PubMed  Google Scholar 

  67. Oliff A, Defeo-Jones D, Boyer M, et al. Tumors secreting human TNF/cachectin induce cachexia in mice.Cell 1987;50:555–63.

    Article  CAS  PubMed  Google Scholar 

  68. Blankenstein TH, Qin Z, Uberla K, Muller W, Rosen H, Volk HD, Diamantstein T. Tumor suppression after tumor cell-targeted tumor necrosis factor alpha gene transfer.J Exp Med 1991;173:1047–52.

    Article  CAS  PubMed  Google Scholar 

  69. Teng MN, Park BH, Koeppen HKW, Tracey KJ, Fendly 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;88:3535–9.

    CAS  PubMed  Google Scholar 

  70. Asher AL, Mule JJ, Kasid A, et al. Murine tumor cells transduced with the gene for tumor necrosis factor-alpha.J Immunol 1991;146:3227–34.

    CAS  PubMed  Google Scholar 

  71. Karp SE, Hwu P, Farber A, Restifo NP, Kriegler M, Mule JJ, Rosenberg SA. In vivo activity of tumor necrosis factor (TNF) mutants: secretory but not membrane-bound TNF mediates the regression of retrovirally transduced murine tumor.J Immunol 1992;149:2076–81.

    CAS  PubMed  Google Scholar 

  72. Hayashi H, Tanaka K, Jay F, Khoury G, Jay G. Modulation of the tumorigenicity of human adenovirus-12-transformed cells by interferon.Cell 1985;43:263–7.

    Article  CAS  PubMed  Google Scholar 

  73. Chen L, Tourvielle B, Burns GF, et al. Interferon: a cytotoxic T lymphocyte differentiation signal.Eur J Immunol 1986;16:767–70.

    CAS  PubMed  Google Scholar 

  74. Maraskovsky E, Chen W-F, Shortman K. IL-2 and IFN-γ are two necessary lymphokines in the development of cytotoxic T cells.J Immunol 1989;143:1210–4.

    CAS  PubMed  Google Scholar 

  75. Watanabe Y, Kuribayashi K, Miyatake S, et al. Exogenous expression of mouse interferon γ cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity.Proc Natl Acad Sci USA 1989;86:9456–60.

    CAS  PubMed  Google Scholar 

  76. Azuma A, Yagita H, Matsuda H, Okumura K, Niitani H. Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell lines by γ-interferon enhances spontaneous and bispecific anti-CD3 X antitumor antibody-directed lymphokine-activated killer cell cytotoxicity.Cancer Res 1992;52:4890–4.

    CAS  PubMed  Google Scholar 

  77. Beniers AJMC, Peelen WP, Debruyne FMJ, Schalken JA. HLA-class-I and class-II expression on renal tumor xenografts and the relation to sensitivity for α-IFN, γ-IFN and TNF.Int J Cancer 1991;48:709–16.

    CAS  PubMed  Google Scholar 

  78. Balkwill FR. Interferons.Lancet 1989;1:1060–3.

    CAS  PubMed  Google Scholar 

  79. Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA. Induction by IL 1 and interferon-γ: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1).J Immunol 1986;137:245–54.

    CAS  PubMed  Google Scholar 

  80. Wadler S, Schwartz EL. Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: a review.Cancer Res 1990;50:3473–86.

    CAS  PubMed  Google Scholar 

  81. Kelly SA, Gschmeissner S, East N, Balkwill FR. Enhancement of metastatic potential by γ-IFN.Cancer Res 1991;51:4020–7.

    CAS  PubMed  Google Scholar 

  82. Porgador A, Bannerji R, Watanabe Y, Feldman M, Gilboa E, Eisenbach L. Antimetastatic vaccination of tumor-bearing mice with two types of IFN-γ gene-inserted tumor cells.J Immunol 1993;150:1458–70.

    CAS  PubMed  Google Scholar 

  83. Restifo NP, Spiess PJ, Karp SE, Mule JJ, Rosenberg SA. A nonimmunogenic sarcoma transduced with the cDNA for interferon γ elicits CD8 T cells against the wildtype tumor: correlation with antigen presentation capability.J Exp Med 1992;175:1423–31.

    Article  CAS  PubMed  Google Scholar 

  84. Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Giboa E. Retroviral vector-mediated γ-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity.Cancer Res 1990;50:7820–5.

    CAS  PubMed  Google Scholar 

  85. Tanaka K, Yoshioka T, Bieberich C, Jay G. Role of the major histocompatability complex class I antigens in tumor growth and metastasis.Ann Rev Immunol 1988;6:369–80.

    Article  Google Scholar 

  86. Esumi N, Hunt B, Itaya T, Frost P. Reduced tumorigenicity of murine tumor cell secreting γ-interferon is due to nonspecific host responses and is unrelated to class I major histocompatability complex expression.Cancer Res 1991;51:1185–9.

    CAS  PubMed  Google Scholar 

  87. Borden EC, Hogan TF, Voelkel JG. Comparative antiproliferative activity in vitro of natural interferons α and β for diploid and transformed human cells.Cancer Res 1982;42:4948–53.

    CAS  PubMed  Google Scholar 

  88. Fidler IH, Heicappell R, Saiki I, Grutter MG, Horisberger MA, Nuesch J. Direct antiproliferative effects of recombinant human interferon-a B/D hybrids on human tumor cell lines.Cancer Res 1987;47:2020–7.

    CAS  PubMed  Google Scholar 

  89. Greiner JW, Guadagni F, Noguchi P, et al. Recombinant interferon enhances monoclonal antibody-targeting of carcinoma lesions in vivo.Science 1987;235:895–8.

    CAS  PubMed  Google Scholar 

  90. Figlin RA, Belldegrun A, Moldawer N, Zeffrin J, De-Kernion JB. Concomitant administration of recombinant human interleukin-2 and recombinant interferon alfa-2A: an active outpatient regimen in metastatic renal cell carcinoma.J Clin Oncol 1992;10:414–21.

    CAS  PubMed  Google Scholar 

  91. Oberg K, Norheim I, Alm G. Treatment of malignant carcinoid tumors: a randomized controlled study of streptozocin plus 5-FU and human leukocyte interferon.Eur J Cancer Clin Oncol 1989;25:1475–9.

    CAS  PubMed  Google Scholar 

  92. Quesada JR, Talpaz M, Rios A, Kurzrock R, Gutterman JU. Clinical toxicity of interferons in cancer patients: a review.J Clin Oncol 1986;4:234–43.

    CAS  PubMed  Google Scholar 

  93. Ferrantini M, Proietti E, Santodonato L, et al. 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;53:1107–12.

    CAS  PubMed  Google Scholar 

  94. Dinarello CA. Interleukin-1 and Interleukin-1 antagonism.Blood 1991;77:1627–52.

    CAS  PubMed  Google Scholar 

  95. Atkins E. Pathogenesis of fever.Physiol Rev 1960;40:580–646.

    CAS  PubMed  Google Scholar 

  96. Oppenheim JJ, Kovacs EJ, Matsushima K, Durum SK. There is more than one interleukin-1.Immunol Today 1986;7:45–54.

    Article  CAS  Google Scholar 

  97. Burrows FJ, Haskard DO, Hart IR, et al. Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro.Cancer Res 1991;51:4768–75.

    CAS  PubMed  Google Scholar 

  98. Delwel R, van Buitenen C, Salem M, et al. Interleukin-1 stimulates proliferation of acute myeloblastic leukemia cells by induction of granulocyte-macrophage colony-stimulating factor release.Blood 1989;74:586–93.

    CAS  PubMed  Google Scholar 

  99. Kaye J, Gillis S, Mizel SB, et al. Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2.J Immunol 1984;133:1339–45.

    CAS  PubMed  Google Scholar 

  100. Zoller M, Douvdevani A, Segal S, Apte RN. Interleukin-1 produced by tumorigenic fibroblasts influences tumor rejection.Int J Cancer 1992;50:443–50.

    CAS  PubMed  Google Scholar 

  101. Dinarello CA, Cannon JG, Wolff SM, et al. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1.J Exp Med 1986;163:1433–50.

    Article  CAS  PubMed  Google Scholar 

  102. Sisson SD, Dinarello CA. Production of interleukin-1a, interleukin-lb and tumor necrosis factor by human mononu-clear cells stimulated with granulocyte-macrophage colony-stimulating factor.Blood 1988;72:1368–74.

    CAS  PubMed  Google Scholar 

  103. Douvdevani A, Huleihel M, Zoller M, Segal S, Apte RN. Reduced tumorigenicity of fibrosarcomas which constitutively generate IL-1a either spontaneously or following IL-1a gene transfer.Int J Cancer 1992;51:822–30.

    CAS  PubMed  Google Scholar 

  104. Zoller M, Douvdevani A, Segal Shraga Apte RN. Interleukin-1 production by transformed fibroblasts. II. Influence on antigen presentation and T-cell-mediated anti-tumor response.Int J Cancer 1992;50:450–7.

    CAS  PubMed  Google Scholar 

  105. Iho S, Shau H, Golub SH. Characteristics of interleukin-6-enhanced lymphokine-activated killer cell function.Cell Immunol 1991;135:66–77.

    Article  CAS  PubMed  Google Scholar 

  106. Luger TA, Krutmann J, Kirnbauer R, et al. IFN-β2/IL-6 augments the activity of human natural killer cells.J Immunol 1989;143:1206–9.

    CAS  PubMed  Google Scholar 

  107. Jablons DM, Mule JJ, McIntosh JK, et al. IL-6/IFN-β-2 as a circulating hormone: induction by cytokine administration in humans.J Immunol 1989;142:1542–7.

    CAS  PubMed  Google Scholar 

  108. Van Snick J. Interleukin-6: an overview.Annu Rev Immunol 1990;8:253–78.

    Article  PubMed  Google Scholar 

  109. Lu C, Vickers ME, Kerbel RS. Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression.Proc Natl Acad Sci USA 1992;89:9215–9.

    CAS  PubMed  Google Scholar 

  110. Mullen CA, Coale MM, Levy AT, et al. Fibrosarcoma cells transduced with the IL-6 gene exhibit reduced tumorigenicity, increased immunogenicity, and decreased metastatic potential.Cancer Res 1992;52:6020–4.

    CAS  PubMed  Google Scholar 

  111. Porgador A, Tzehoval E, Katz A, et al. Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells.Cancer Res 1992;52:3679–86.

    CAS  PubMed  Google Scholar 

  112. Chen L, Mory Y, Zilberstein A, Revel M. Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferon-b2.Proc Natl Acad Sci USA 1988;85:8037–41.

    CAS  PubMed  Google Scholar 

  113. Lavey RL, McBride WH, Comora SM, et al. Effect of interleukin-6 on tumor cell growth in vivo and in vitro. In: Revel M, ed.IL-6: pathological and clinical potentials. New York: Raven, 1992:273–80.

    Google Scholar 

  114. Mule JJ, McIntosh JK, Jablons DM, Rosenberg SA. Antitumor activity of recombinant interleukin 6 in mice.J Exp Med 1990;171:629–36.

    Article  CAS  PubMed  Google Scholar 

  115. Rich BE, Campos-Torres J, Tepper RI, Moreadith RW, Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice.J Exp Med 1993;177:305–16.

    Article  CAS  PubMed  Google Scholar 

  116. Welch PA, Namen AE, Goodwin RG, Armitage R, Cooper MD. Human IL-7: a novel T cell growth factor.J Immunol 1989;143:3562–7.

    CAS  PubMed  Google Scholar 

  117. Dubinett SM, Huang M, Dhanani S, McBride WH. Interleukin 7 down-regulates fibrosarcoma production of transforming growth factor-β.Proc Am Assoc Cancer Res 1993;34:462.

    Google Scholar 

  118. Lynch DH, Namen AE, Miller RE. In vivo evaluation of the effects of interleukins 2, 4 and 7 on enhancing the immunotherapeutic efficacy of anti-tumor T lymphocytes.Eur J Immunol 1991;21:2977–85.

    CAS  PubMed  Google Scholar 

  119. McBride WH, Thacker JD, Comora S, et al. Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity.Cancer Res 1992;52:3931–7.

    CAS  PubMed  Google Scholar 

  120. Hock H, Dorsch M, Diamantstein T, Blankenstein T. Interleukin 7 induces CD4+ T cell-dependent tumor rejection.J Exp Med 1991;174:1291–8.

    Article  CAS  PubMed  Google Scholar 

  121. Aoki T, Tashiro K, Miyatake S-I, et al. Expression of murine interleukin 7 in a murine glioma cell line results in reduced tumorigenicity in vivo.Proc Natl Acad Sci USA 1992;89:3850–4.

    CAS  PubMed  Google Scholar 

  122. Wolf SF, Temple PA, Kobayashi M, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells.J Immunol 1991;146:3074–81.

    CAS  PubMed  Google Scholar 

  123. Schoenhaut DS, Chua AO, Wolitzky AG, et al. Cloning and expression of murine IL-12.J Immunol 1992;148:3433–40.

    CAS  PubMed  Google Scholar 

  124. Gately MK. Interleukin-12. A recently discovered cytokine with potential for enhancing cell-mediated immune responses to tumors.Cancer Invest 1993;11:500–6.

    CAS  PubMed  Google Scholar 

  125. Tripp CS, Wolf SA, Unanue ER. Interleukin 12 and tumor necrosis factor a are costimulators of intereron γ production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist.Proc Natl Acad Sci USA 1993;90:3725–9.

    CAS  PubMed  Google Scholar 

  126. D'Andrea A, Rengaraju M, Valiante NM, et al. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.J Exp Med 1992;176:1387–98.

    Article  PubMed  Google Scholar 

  127. Germann T, Gately MK, Schoenhaut DS, et al. Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells.Eur J Immunol 1993;23:1762–70.

    CAS  PubMed  Google Scholar 

  128. Brunda MJ, Luistro L, Warrier R, et al. Antitumor and antimetastatic activity of interleukin-12 against murine tumors.J Exp Med 1993;178:1223–30.

    Article  CAS  PubMed  Google Scholar 

  129. Tahara H, Zeh H III, Pappo I, Nastala C, Robbins PD, Lotze MT. Suppressed growth of murine melanoma in vivo with local secretion of interleukin-12 delivered by transfected fibroblasts.Proc Am Assoc Cancer Res 1993;34:463.

    Google Scholar 

  130. Einerhand MPW, Bakx TA, Kukler A, Valerio D. Factors affecting the transduction of pluripotent hematopoietic stem cells: long-term expression of a human adenosine deaminase gene in mice.Blood 1993;81:254–63.

    CAS  PubMed  Google Scholar 

  131. Schrader JW. The panspecific hemopoietin of activated T lymphocytes (interleukin 3).Ann Rev Immunol 1986;4:205–30.

    Article  CAS  Google Scholar 

  132. Pulaski BA, McAdam AJ, Hutter EK, Biggar S, Lord EM, Frelinger JG. Interleukin 3 enhances development of tumor-reactive cytotoxic cells by a CD4-dependent mechanism.Cancer Res 1993;53:2112–7.

    CAS  PubMed  Google Scholar 

  133. Moore MAS. The clinical use of colony stimulating factors.Annu Rev Immunol 1991;9:159–91.

    Article  CAS  PubMed  Google Scholar 

  134. Colombo MP, Ferrari G, Stoppacciaro A, et al. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo.J Exp Med 1991;173:889–97.

    Article  CAS  PubMed  Google Scholar 

  135. Tani K, Ozawa K, Ogura H, et al. Implantation of fibroblasts transfected (calcium phosphate) with human granulocyte colony-stimulating factor cDNA into mice as a model of cytokine-supplement gene therapy.Blood 1989;74:1274–80.

    CAS  PubMed  Google Scholar 

  136. Miller AR, McBride WH, Moen RC, Schuck BL, Glasby JA, Economous JS. Interleukin-2 producing fibroblast cell line abrogates tumorigenicity in a murine tumor model: an approach to genetically engineered tumor vaccines.Surg Forum 1993;44:512–4.

    Google Scholar 

  137. Gasson JC, Weisbart RH, Kaufman SE, et al. Purified human granulocyte-macrophage colony-stimulating factor: direct action on neutrophils.Science 1984;226:1339–42.

    CAS  PubMed  Google Scholar 

  138. Wong GG, Witek JS, Temple PA, et al. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant products.Science 1985;228:810–5.

    CAS  PubMed  Google Scholar 

  139. Steinman RM. The dendritic cell system and its role in immunogenicity.Annu Rev Immunol 1991;9:271–96.

    Article  CAS  PubMed  Google Scholar 

  140. Heidenreich S, Gong J-H, Schmidt A, Nain M, Gemsa D. Macrophage activation by granulocyte/macrophage colony stimulating factor.J Immunol 1989;143:1198–205.

    CAS  PubMed  Google Scholar 

  141. Vadas MA, Nicola NA, Metcalf D. Activation of antibody-dependent cell-mediated cytotoxicity of human neutrophils and eosinophils by separate colony-stimulating factors.J Immunol 1983;130:795–9.

    CAS  PubMed  Google Scholar 

  142. Antman KS, Griffin JD, Elias A, et al. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression.N Engl J Med 1988;319:593–8.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. From the Department of Surgery and Radiation Oncology, UCLA Medical Center, Los Angeles, California, USA

    Alexander R. Miller MD, William H. McBride PhD, DSc, Kelly Hunt MD &  James S. Economou MD, PhD (FACS)

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  1. Alexander R. Miller MD
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  2. William H. McBride PhD, DSc
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  3. Kelly Hunt MD
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  4. James S. Economou MD, PhD
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Miller, A.R., McBride, W.H., Hunt, K. et al. Cytokine-mediated gene therapy for cancer. Annals of Surgical Oncology 1, 436–450 (1994). https://doi.org/10.1007/BF02303818

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