Ovarian Cancer pp 133-157 | Cite as

Gene Therapy

  • Warner K. Huh
  • Mack N. Barnes
  • F. Joseph Kelly
  • Ronald D. Alvarez
Part of the Cancer Treatment and Research book series (CTAR, volume 107)


Ovarian carcinoma continues to be the most common cause of death from gynecologic malignancy in the United States. This high fatality rate can be attributed to a lack of early, effective screening strategies and lack of specific symptoms associated with early stage disease. Thus, approximately 70% of women with ovarian cancer present with advanced stage disease. Although advances in surgical therapy and chemotherapy have improved progression free survival, the long-term 5-year survival rate rarely exceeds 30% for patients diagnosed with this disease (1).


Ovarian Cancer Gene Therapy Ovarian Carcinoma Ovarian Cancer Cell Ovarian Cancer Patient 
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  1. 1.
    Crawford R, Shephard J. Management of Epithelial Ovarian Cancer. In: Shingleton H, Fowler W, Jordan J, Lawrence W, eds. Gynecologic Oncology: Current Diagnosis and Treatment. London: W B Saunders, 203–212, 1996.Google Scholar
  2. 2.
    Kinzler KW and Vogelstein B: Lessons from hereditary colorectal cancer. Cell 1996; 87: 159–170.PubMedCrossRefGoogle Scholar
  3. 3.
    Kinzler KW and Vogelstein B: Landscaping the cancer terrain. Science 1998; 280: 1036–1037.PubMedCrossRefGoogle Scholar
  4. 4.
    Hirschowitz E, Ohwada A, Pasca W, Russi T, Crystal R. In vivo adenovirus-mediated geneGoogle Scholar
  5. 5.
    transfer of the Eschrichia Coli cytosine deaminase gene to human colon carcinomaderived tumors induces chemosensitivity to 5-fluorocytosine. Human Gene Ther 1995;6:1055–63.Google Scholar
  6. 6.
    Elion G, Furman P, Fyfe J, DeMiranda P, Beauchamp L, Schaeffer H. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci USA 1977; 74: 5716–20.PubMedCrossRefGoogle Scholar
  7. 7.
    Furman P, McGujirt P, Keller P, Fyfe J, Elion G. Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with herpes virus genetic information. Virology 1980; 102: 420–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Abe A, Takeo T, Emi N, Tanimoto M, Ueda R, Yee J, et al. Transduction of a drug-sensitive toxic gene into human leukemia cell lines with a novel retroviral vector. PSEMB 1993; 203: 354–8.Google Scholar
  9. 9.
    Culvert K, Ram Z, Walbridge S, Ishii H, Oldfield E, Blaese R. In vivo gene transfer with retroviral vector-producing cells for the treatment of experimental brain tumors. Science 1992; 256: 1550–52.CrossRefGoogle Scholar
  10. 10.
    Vile R, Nelson J, Castleden S,Chong H, Hart I. Systemic gene therapy of murine melanoma using tissue specific expression of the HSV-tk gene involves an immune component. Cancer Res 1994; 54: 6228–34.PubMedGoogle Scholar
  11. 11.
    Mesnil M, Piccoli C, Tiraby G, Willecke K, Yamasaki H. Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins. Proc Natl Acad Sci USA 1996; 93: 1831–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Gagandeep S, Brew R, Green B, et al. Prodrug-activated gene therapy: Involvement of an immunological component in the `bystander’ effect. Cancer Gene Therapy 1996; 3: 83–88.PubMedGoogle Scholar
  13. 13.
    Consalvo M, Mullen Ca, Modesti A, et al. 5-fluorocyostine induced eradication of murine adenocarcinoma engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory. J Immunology 1995; 154: 5302–5312.Google Scholar
  14. 14.
    Freeman S, Abboud C, Whartenby K, Packman C, Koeplin D, Moolten F, et al. The “bystander effect”: Tumor regression when a fraction of the tumor mass is genetically modified.Cancer Res 1993; 53: 5274–83.Google Scholar
  15. 15.
    Robinson W, Adams J, Marrogi A, Freeman S. Vaccine therapy for ovarian cancer using herpes simplex virus thymidine kinase (HSV-TK) suicide gene transfer technique: A phase I study. Gynecol Oncol 1998; 68: 88.Google Scholar
  16. 16.
    Link C, Moorman D. Clinical protocols: A phase I trial of in vivo gene therapy with the Herpes Simplex Thymidine Kinase/Ganciclovir system for the treatment of refractory of recurrent ovarian cancer. Cancer Gene Ther 1995; 2: 230–1.Google Scholar
  17. 17.
    Link C, Eldeman M, Tennant L, et al. LTKOSN.1 murine vector producer cell(VPC) for the in vivo delivery of the herpes simplex thymidine kinase (HSV-TK) gene for ovarian cancer. Am Soc Gene Ther Abstract #915 (1999).Google Scholar
  18. 18.
    Rosenfeld ME, Feng M, Michael SI, et al. Adenoviral-mediated delivery of the herpes simples virus thymidine kinase gene selectively sensitizes human ovarian carcinoma cells to ganciclovir. Clin Cancer Research 1995; 1: 1571–1580.Google Scholar
  19. 19.
    Rosenfeld ME, Wang M, Siegal GP, et al. Adenoviral-mediated delivery of herpes simplex virus thymidine kinase results in tumor reduction and prolonged survival in a SCID mouse model of human ovarian carcinoma. J Mol Med 1996; 74: 455–462.PubMedCrossRefGoogle Scholar
  20. 20.
    Alvarez R, Gomez-Navarro J, Wang M, et al. Adenoviral mediated suicide gene therapy for ovarian cancer (No. 107) Gynecol Oncol 2000; 76: 258.Google Scholar
  21. 21.
    Quattrone A, Fibbi G, Anichini E, Pucci M, Zamperini A, Capaccioli S, et al. Reversion of the invasive phenotype of transformed human fibroblasts by anti-messenger oligonucleotide inhibition of urokinase receptor gene expression. Cancer Res 1995; 55: 90–5.PubMedGoogle Scholar
  22. 22.
    Shaw Y, Chang S, Chiou S, Chang W, Lai M. Partial reversion of transformed phenotype of B104 cancer cells by antisense nucleic acids. Cancer Letters 1993; 69: 27–32.PubMedCrossRefGoogle Scholar
  23. 23.
    Douglas J, Curiel D. Targeted gene therapy. Tumor Targeting 1995; 1: 67–84.Google Scholar
  24. 24.
    Helm C, Shrestha K, Thomas S, Shingleton H, Miller D. A unique c-myc-targeted triplex-forming oligonucleotide inhibits the growth of ovarian and cervical carcinomas in vitro. Gynecol Oncol 1993; 49: 339–43.PubMedCrossRefGoogle Scholar
  25. 25.
    Durland R, Kessler D, Gunnell S, Duvic M, Pettitt B, Hogan M. Binding of triplex helix-forming oligonucleotides to sites in gene promoters. Biochemistry 1991; 30: 9246–55.PubMedCrossRefGoogle Scholar
  26. 26.
    Ebbinghouse S, Gee J, Rodu B, Mayfield C, Sanders G, Miller D. Triplex formation inhibits HER-2/neu transcription in vitro. J Clin Invest 1993; 92: 2433–9.CrossRefGoogle Scholar
  27. 27.
    Mayfield C, Ebbinghouse S, Gee J, Jones D, Rodu B, Squibb M, et al. Triplex formation by the human H-ras promoter inhibits Spl binding and in vitro transcription. J Biol Chem 1994; 269: 18232–8.PubMedGoogle Scholar
  28. 28.
    Mayfield C, Squibb M, Miller D. Inhibition of nuclear protein binding to the human Ki-ras promoter by triplex-forming oligonucleotides. Biochemistry 1994; 33: 3358–63.PubMedCrossRefGoogle Scholar
  29. 29.
    Mukhopadhyay T, Tainsky M, Cavender A, RothJ. Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. Cancer Res 1991; 51: 1744–8.PubMedGoogle Scholar
  30. 30.
    Georges R, Mukhopadhyay T, Zhang Y, Yen N, Roth J. Prevention of orthotopic human lung cancer growth by intratracheal instillation of a retroviral antisense K-ras construct. Cancer Res 1993; 53: 1743–6.PubMedGoogle Scholar
  31. 31.
    Saison-Behmoaras T, Tocque B, Rey I, Chassignol M, Thuong N, Helene,C. Short modified antisense oligonucleotide directed against Ha-ras point mutation induces selective cleavage of the mRNA and inhibits T24 cell proliferation. EMBO J 1991; 30: 1111–6.Google Scholar
  32. 32.
    Calabretta B, Sims R, Valtieri M, Caracciolo D, Szczylik C, Venturelli D, et al. Normal and leukemic hematopoietic cells manifest differential sensitivity to inhibitory effects of c-myb antisense oligodeoxynucleotides: An in vitro study relevant to bone marrow purging. Proc Natl Acad Sci USA 1991; 88: 2351–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Ratajczak M, Kant J, Luger S, Hijiya N, Zhang J, Zon G, et al. In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligonucleotides. Proc Natl Acad Sci USA 1992; 89: 11823–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Wickstrom E, Bacon T, Gonzalez A, Freeman D, Lyman G, Wickstrom E. Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc RNA. Proc Natl Acad Sci USA 1988; 85: 1028–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Harel-Ballan A, Ferris D, Vinocour M, Holt J, Farrar W. Specific inhibition of c-myc protein biosynthesis using an antisense synthetic deoxynucleotide in human T lymphocytes. J Immunol 1988; 140: 2431–5.Google Scholar
  36. 36.
    McManaway M, Neckers L., Loke S., Al-Nasser A, Redner R, Shiramizu B, et al. Tumour-specific inhibition of lymphoma growth by an antisense oligodeoxynucleotide. Lancet 1990; 35: 808–11.CrossRefGoogle Scholar
  37. 37.
    Collins J, Herman P, Schuch C, Bagby G. c-myc antisense oligonucleotides inhibit the colony-forming capacity of Colo 320 colonic carcinoma cells. J Clin Invest 1992; 89: 1523–27.PubMedCrossRefGoogle Scholar
  38. 38.
    Janicek M, Sevin B, Nguyen H, Averette H. Combination anti-gene therapy targeting cmyc and p53 in ovarian cancer cell lines. Gynecol Oncol 1995; 59: 87–92.PubMedCrossRefGoogle Scholar
  39. 39.
    Neuenschwander S, Roberts C, LeRoith D. Growth inhibition of MCF-7 breast cancer cells by stable expression of an insulin-like growth factor 1 receptor antisense ribonucleic acid. Endocrinology 1995; 136: 4298–303.PubMedCrossRefGoogle Scholar
  40. 40.
    Resnicoff M, Abraham D, Yutanawiboonachi W, Rotman H, Kajstura J, Rubin R, et al. The insulin-like growth factor 1 receptor protects tumor cells from apoptosis in vivo. Cancer Res 1995; 55: 2463–9.PubMedGoogle Scholar
  41. 41.
    Resnicoff M, Ambrose D, Coppola D, Rubin R. Insulin-like growth factor-1 and its receptor mediate autocrine proliferation of human ovarian carcinoma cell lines. Lab Invest 1993; 69: 756–60.PubMedGoogle Scholar
  42. 42.
    Szczylik T, Skorski T, Nicolaides N, Manzella L., Malaguamera L., Venturelli D, et al. Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. Science 1991; 253: 562–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Skorski T, Nieborowska-Skorska M, Nicolaides N, Szczylik C, Iversen P, Iozzo R, et al. Suppression of Philadelphia leukemia cell proliferation in mice by BCR-ABL antisense oligodeoxynucleotide. Proc Natl Acad Sci USA 1994; 91: 4504–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Kashani-Sabet M, Funato T, Florenes V, Fodstad O, Scanlon K. Suppression of the neoplastic phenotype in vivo by an anti-ras ribozyme. Cancer Res 1994; 54: 900–2.PubMedGoogle Scholar
  45. 45.
    Kashani-Sabet M, Funato T, Tone T, Jiao L, Wang W, Yashida E, et al. Reversal of the malignant phenotype by an anti-ras ribozyme. Antisense Res Dev 1992; 2: 3–15.PubMedGoogle Scholar
  46. 46.
    Lange W, Cantin E, Finke J, Dolken G. In vitro and in vivo effects of synthetic ribozymes targeted against BCR/ABL mRNA. Leukemia 1993; 7: 1786–94.PubMedGoogle Scholar
  47. 47.
    Snyder D, Wu Y, Wang J, Rossi J, Swiderski P, Kaplan B, et al. Ribozyme mediated inhibition of bcr-abl gene expression in a Philadelphia chromosome-positive cell line. Blood 1993; 82: 600–5.PubMedGoogle Scholar
  48. 48.
    Milner B, Allan L, Eccles D,et al. p53 mutation is a common genetic event in ovarian carcinoma. Cancer Res 1993; 53: 2128–2132.PubMedGoogle Scholar
  49. 49.
    Porter P, gown A, Kramp S, et al. Widespread p53 overexpression in human malignant tumors. Am J Pathol 1992; 140: 145–153.PubMedGoogle Scholar
  50. 50.
    Santoso JT, Tang DC, Lane SB, et al. Adenovirus-based p53 gene therapy in ovarian cancer. Gynecol Oncol 1995; 59: 171–178.PubMedCrossRefGoogle Scholar
  51. 50.
    Mujoo K, Maneval DC, Anderson SC, et al. Adenoviral-mediated p53 tumor suppressor gene therapy of human ovarian carcinoma. Oncogene 1996; 12: 1617–1623.PubMedGoogle Scholar
  52. 51.
    Janicek M, Sevin B, Nguyen H, Averette H. Combination anti-gene therapy targeting cmyc and p53 in ovarian cancer cell lines. Gynecol Oncol 59: 87, 1995PubMedCrossRefGoogle Scholar
  53. 52.
    Wolf J, Mills G, Bazzet L et al. Adenovirus mediated p53 growth inhibition of ovarian cancer cells is independent of endogenous p53 status. Gynecol Oncol 75: 261, 1999.PubMedCrossRefGoogle Scholar
  54. 53.
    Holt JT, Thompson Me, Szabo C, et al. Growth retardation and tumour inhibition by BRCA1. Nature Genetics 1996; 12: 223–225.CrossRefGoogle Scholar
  55. 54.
    Song K, Cowan K, Sinha B. In vivo studies of adenovirus-mediated p53 gene therapy for cis-platin resistant human ovarian tumor xenografts. Oncology Res 1999; 11: 153.Google Scholar
  56. 55.
    Nielsen L, Lipari P, Dell J, et al. Adenovirus mediated p53 gene therapy and paclitaxel have synergistic efficacy in models of human head and neck, ovarian, prostate, and breast cancer. Clin Cancer Res 1998; 4: 835.PubMedGoogle Scholar
  57. 56.
    Minaguchi T, Mori T, Kanamori Y, et al. Growth suppression of human ovarian cancer cells by adenovirus mediated transfer of the PTEN gene. Cancer Res 1999 59: 6063.PubMedGoogle Scholar
  58. 57.
    Wolf J, Kim T, Fightmaster D, et al. Growth suppression of human ovarian cancer cell lines by the introduction of a p16 gene via a recombinant adenovirus. Gynecol Oncol 1999; 73: 27.PubMedCrossRefGoogle Scholar
  59. 58.
    Xiang J, Piche A, Gomez-Navarro J, Siegal, GP, Alvarez RD, Curiel DT: An inducible recombinant adenoviral vector encoding bax selectively induces apoptosis in ovarian cancer cells. Tumor Targeting 4: 1–9, 1999.Google Scholar
  60. 59.
    Tai Y, Strobel T, Kufe D, Cannistra S. In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the BAX gene. Cancer Res 59: 2121, 1999.PubMedGoogle Scholar
  61. 60.
    Xiang J, Gomez-Navarro J, Arafat W, Liu B, Parker S, Alvarez R, Siegal G, Curie! D: Proapoptotic treatment with an adenovirus encoding bax enhances the effect of chemotherapy in ovarian cancer: J Gene Medicine 2: 97–106, 2000.Google Scholar
  62. 61.
    Arafat WO, Gomez-Navarro J, Xiang J, Barnes M, Mahareshti P, Alvarez RD, Siegal, GP, Badib AO, Buchsbaum D, Curiel DT, Stackhouse MA: An adenovirus encoding proapoptotic bax induces apoptosis and enhances the radiation effect in human ovarian cancer. Molecular Therapy 1: 1–7, 2000.CrossRefGoogle Scholar
  63. 62.
    Redemann N, Holzmann B, von Ruden T, Wagner E, Schlessinger J, Ullrich A. Antioncogenic activity of signalling-defective epidermal growth factor receptor mutants. Mol Cell Biol 1992; 12: 491–8.PubMedGoogle Scholar
  64. 63.
    Ueno H, Colbert H, Escobedo J, Williams L. Inhibition of PDGF beta receptor signal transduction by coexpression of a truncated receptor. Science 1991: 252: 844–8.PubMedCrossRefGoogle Scholar
  65. 64.
    Prager D, Li H, Asa S, Melmed S. Dominant-negative inhibition of tumorigenesis in vivo by human insulin-like growth factor I receptor mutant. Proc Natl Acad Sci USA 1994; 91: 2181–5.PubMedCrossRefGoogle Scholar
  66. 65.
    Millauer B, Shawver L, Plate K, Risau W, Ullrich A. Glioblastoma growth inhibited in vivo by a dominant-negativeflk -1 mutant. Nature 1994; 367: 576–9.PubMedCrossRefGoogle Scholar
  67. 66.
    Shamah S, Stiles C, Guha A. Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. Mol Cell Biol 1993; 12: 1674–9.Google Scholar
  68. 67.
    Deshane J, Loechel F, Conry R, Siegal G, King C, Curiel D. Intracellular single-chain antibody directed against erbB-2 down-regulates cell surface erbB-2 and exhibits a selective antiproliferative effect in erbB-2 overexpressing cancer cell lines. Gene Ther 1994; 3: 332–7.Google Scholar
  69. 68.
    Beerli R, Winfried W, Hynes N. Intracellular expression of single chain antibodies reverts erbB-2 transformation. J Biol Chem 1994; 269: 23931–6.PubMedGoogle Scholar
  70. 69.
    Deshane J, Grim J, Loechel S, Siegal G, Alvarez R, King C, et al. Intracellular antibody directed against erbB-2 mediates targeted tumor cell eradication by inducing apoptosis.Cancer Gene Ther 1996; 3: 89–98.Google Scholar
  71. 70.
    Beerli R, Wels W, Hynes N. Autocrine inhibition of the epidermal growth factor receptor by intracellular expression of a single-chain antibody. Biochem and Biophys Res Comm 1994; 204: 666–72.CrossRefGoogle Scholar
  72. 71.
    Tait D, Obermiller P, Frazier S, et al. A Phase I trial of retroviral BRCA 1 sv gene therapy in ovarian cancer. Clin Cancer Res 1997; 3: 1959.PubMedGoogle Scholar
  73. 72.
    Buller R, Pegram M, Runnebaum I, A Phase I/H trial of recombinant adenovrial human p53 intraperitoneal gene therapy in recurrent ovarian cancer (No. 37) Gynecol Oncol 1999; 72: 452.Google Scholar
  74. 73.
    Zhang Y, Yu D, Xia W, Hung M. HER-2/neu targeting cancer therapy via adenovirusmediated E 1 A delivery in an animal model. Oncogene 1995; 10: 1947–54.Google Scholar
  75. 74.
    Ueno N, Bartholomeusz C, Herrmann J, et al. ElA mediated paclitaxel sensitization in HER-2/neu overexpressing ovarian cancer SKOV-3.ipl through apoptosis involving the caspase-3 pathway. Clin Cancer Res 2000; 6: 250.PubMedGoogle Scholar
  76. 75.
    Barnes M, Deshane J, Siegal G, et al. Novel gene therapy strategies to accomplish growth factor modulation induces enhanced tumor cell chemosensitivity. Clin Cancer Res 1996; 2: 1089.PubMedGoogle Scholar
  77. 76.
    Sahin U, Tureci O, Schmitt H et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 1995; 92: 11810–11813.PubMedCrossRefGoogle Scholar
  78. 77.
    Peoples GE, Goedegeguure PS, Smith R, et al. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER-2/neu-derived peptide. Proc Natl Acad Sci USA 1995; 92: 432–436.PubMedCrossRefGoogle Scholar
  79. 78.
    Ionnaides CG, Fisk B, Fan D, et al. Cytotoxic T cells isolated from ovarian malignant ascites recognize a peptide derived from the HER-2/neu protooncogene. Cell Immunol 1993; 151: 225–234.CrossRefGoogle Scholar
  80. 79.
    Merogi AJ, Marrogi Ai, Ramesh R, et al. Tumor-host interation: Analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinoma. Hum Pathol 1997; 38: 321–331.CrossRefGoogle Scholar
  81. 80.
    Kooi S, zhang HZ, Patenia R, et al. HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2. Cell Immunol 1996; 174: 116–118.PubMedCrossRefGoogle Scholar
  82. 81.
    Stancovski I, Schinder DG, Waks T, et al. Targeting of T lymphocytes to neu/HER-2expressing cells using chimeric single chain Fv receptors. J Immunol 1993; 151: 65776582.Google Scholar
  83. 82.
    Eshhar Z, Waks T, Gross G, et al. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the and s ubunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA 1993; 90: 720–724.PubMedCrossRefGoogle Scholar
  84. 83.
    Hwu P, Shafer GE, Treisman J, et al. Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and Fc receptor gamma chain. J Exp Med 1993; 178: 361–366.PubMedCrossRefGoogle Scholar
  85. 84.
    Yannelli J, Hyatt C, Johnston S, Hwu P, Rosenberg S. Characterization of human tumour cell lines transduced with the cDNA encoding either tumor necrosis factor a (TNF-a or interleukin-2 (IL-2). J Immunol Methods 1993; 161: 77–90.PubMedCrossRefGoogle Scholar
  86. 85.
    Fearon ER, Pardoll DM, Itaya T, et al Interluekin -2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 1990; 60: 397–403.PubMedCrossRefGoogle Scholar
  87. 86.
    Blankenstein T, Qin Z, Uberla K et al. Tumor suppression after tumor cell-targetedd tumor necrosis factor a gene transfer. J Exp Med 1991; 173: 1047–1052.PubMedCrossRefGoogle Scholar
  88. 87.
    Lopez-Cepero M, Garcia-Sanz JA, Herbert L, et al. Soluble and membrane-bound TNFalpha are involved in the cytotoxic activity of B cells from tumor-bearing mice against tumor targets. J Immunol 1994; 152: 3333–3341.PubMedGoogle Scholar
  89. 88.
    Lu Y, Ussery DG, Muncaster MM, et al. Evidence for retinoblastoma protein (Rb) dependent and independent IFN-gamma responses: RB coordinately rescues IFN-gamma induction of MHC class II gene transcription in noninducible breast carcinoma cells. Oncogene 1994; 9: 1015–1019.PubMedGoogle Scholar
  90. 89.
    Matory YL, Chen M, Dorfman DM, et al. Antitumor activity of three mouse mammary cancer cell lines after interferon-gamma gene transfection. Surgery 1995; 118: 251–256.PubMedCrossRefGoogle Scholar
  91. 90.
    Tanaka K, Isselbacher KJ, Khoury G, et al. Reversal of oncogenesis by the expression of a major histocompatibility comples class I gene. Science 1985; 228: 26–30.PubMedCrossRefGoogle Scholar
  92. 91.
    Asher A, Mule J, Kasid A, Restifo N, Salo J, Reichart C, et al. 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: 3227–34.PubMedGoogle Scholar
  93. 92.
    Golumbek P, Lazenby A, Levitzky H, Jafee L, Karasuyama H, Baker M, et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 1991; 254: 713–6.PubMedCrossRefGoogle Scholar
  94. 93..
    Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Gilboa E. Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 1990; 50: 7820–5.PubMedGoogle Scholar
  95. 94.
    Tahara H, Lotze M. Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer. Gene Ther 1995; 2: 96–106.PubMedGoogle Scholar
  96. 95.
    Nabel G, Nabel E, Yang Z, Fox B, Plautz G, Gao X, et al. Direct gene transfer with DNA-liposome complexes in melanoma: expression, biological activity, and lack of toxicity in humans. Proc Natl Acad Sci USA 1993; 90: 11307–11.PubMedCrossRefGoogle Scholar
  97. 96.
    Conry R, Lobuglio A, Loechel F, Moore S, Sumerel L, Barlow D, et al. A carcinoembryonic antigen polynucleotide vaccine has in vivo antitumor activity. Gene Ther 1995; 2: 59–65.PubMedGoogle Scholar
  98. 97.
    Disis M, Smith J, Murphy A, Chen W, Cheever M. In vitro generation of human cytolytic T-cells specific for peptides derived from the HER-2/neu protooncogene protein. Cancer Res 1994; 54: 1071–6.PubMedGoogle Scholar
  99. 98.
    Rosenberg S, Packard B, Aebersold P, Solomon D, Topalian S, Toy S, et al. Use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. Preliminary report. N Engl J Med 1988; 319: 1676–80.PubMedCrossRefGoogle Scholar
  100. 99.
    Rosenberg S, Yannelli J, Yang J, Topalian S, Schwartzentruber D, Weber J, et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 1994; 86: 1159–66.PubMedCrossRefGoogle Scholar
  101. 100.
    Hwu P, Shafer G, Treisman J, Schindler D, Gross G, Cowherd R, et al. Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor chain. J Exp Med 1993; 178: 361–6.PubMedCrossRefGoogle Scholar
  102. 101.
    Hwu P, Yang J, Cowherd R, Treisman J, Shafer J, Eshhar Z, Rosenberg S. In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes. Cancer Res 1995; 55: 3369–73PubMedGoogle Scholar
  103. 102.
    Biedler J, Riehm H. Cellular resistance to actinomycin D in chinese hamster cells in vitro: cross resistance, radioautographic, and cytogenetic studies. Cancer Res 1970; 30: 117484.Google Scholar
  104. 103.
    van der Zee A, Hollema H, Suurmeijer A, Krans M, Sluiter W, Willemse P, et al. Value of p-glycoprotein, glutathione S-tranferase pi, c-erbB-2, and p53 as prognostic factors in ovarian cancer. J Clin Oncol 1995; 13: 70–8.PubMedGoogle Scholar
  105. 104.
    Chin K, Tanaka S, Darlington G, Pastan I, Gottesman M. Heat-shock and arsenic increase expression of the multi-drug resistance (MDR1) gene in human renal carcinoma cells. J Biol Chem 1990; 265: 221–6.PubMedGoogle Scholar
  106. 105.
    Chan H, Haddad G, Thomer P, Deboer G, Lin Y, Ondrusek N, Yeger H, Ling V. Pgycoprotein expression as a predictor of the outcome of therapy for neuroblastoma. N Eng J Med 1991; 325: 1608–14.CrossRefGoogle Scholar
  107. 106.
    Holtzmayer T, Hilsenbeck S, Van Hoff D, Roninsonl. Clinical correlates of MDR-1 (Pglycoprotein) gene expression in ovarian and small cell lung carcinomas. J Natl Cancer Inst 1992; 84: 1486–91.CrossRefGoogle Scholar
  108. 107.
    Venelle P, Meissonnier F, Fonck Y, Feillel V, Dionet C, Kwiatkowski F, et al. Clinical relevance of immunohistochemical detection of multidrug resistance p-glycoprotein in breast cancer. J Natl Cancer Inst 1991; 83: 111–6.CrossRefGoogle Scholar
  109. 108.
    Champlin R, Kavanagh J, Deisseroth A. Use of safety-modified retrovirus to introduce chemotherapy resistance sequences into normal hematopoietic cells for chemoprotection during the therapy of ovarian cancer: A pilot trial. Hum Gene Ther 1994; 5: 1507–22.CrossRefGoogle Scholar
  110. 109.
    Endicott J, Ling V. The biochemistry of P-glycoprotein mediated drug resistance. Annu Rev Biochem 1989; 58: 137–71.PubMedCrossRefGoogle Scholar
  111. 110.
    Sorrentino BP, Brandt SJ, Bodine D, et al. Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1. Science 1992; 257: 99–103.PubMedCrossRefGoogle Scholar
  112. 111.
    Bienzle D, Abrams-Ogg AC, Kruth SA, et al. Gene transfer into hematopoetic stem cells: Long term maintenance of in vitro activated progenitors without marrow ablation. Proc Natl Acad Sci USA 1994; 91: 350–354.PubMedCrossRefGoogle Scholar
  113. 112.
    Clarke MF, Apel IJ, Benedict MA, et al. A recombinant bcl-xs adenovirus selectively induces apoptosis in cancer cells but not in normal bone marrow. Proc Natl Acad Sci USA 1995; 92: 11024–11028.PubMedCrossRefGoogle Scholar
  114. 113.
    Kim M, Wright M, DeShane J, et al. A novel gene therapy strategy for elimination of prostate carcinoma cells from human bone marrow. Hum Gene Therapy 1997; 8: 157–170.CrossRefGoogle Scholar
  115. 114.
    Seth P, Brinkmann U, Schwartz GN, et al. Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging. Cancer Res 1996; 56: 1346–1351.PubMedGoogle Scholar
  116. 115.
    Goldstein LJ, Galski H, Fogo A, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 1989; 81: 116–124.PubMedCrossRefGoogle Scholar
  117. 116.
    Schurs E, Raymond M, Bell J, Gros P. Characterization of the multidrug resistance protein expressed in cell clones stably transfected with the mouse mdrl cDNA. Cancer Res 1989; 49: 2729–34.Google Scholar
  118. 117.
    Devault A, Gros P. Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specifities. Mol Cell Biol 1990; 10: 1652–63.PubMedGoogle Scholar
  119. 118.
    Ueda K, Cardarelli C, Gottesman M, Pastan I. Expression of a full-length cDNA for the human “MDR1” gene confers resistance to colchicine, doxrubicin, and vinblastine. Proc Natl Acad Sci USA 1987; 84: 3004–8.PubMedCrossRefGoogle Scholar
  120. 119.
    Goldstein L, Galski H, Fojo A, Willingham M, Lai S, Gadzar A, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 1989; 81: 116–24.PubMedCrossRefGoogle Scholar
  121. 120.
    Pastan I, Gottesman M, Ueda K, Lovelace E, Rutherford A, Willingham M. A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of pglycoprotein in MDCK cells. Proc Natl Acad Sci USA 1988; 85: 4486–90.PubMedCrossRefGoogle Scholar
  122. 121.
    Hanania E, Deisseroth A. Serial transplantation shows that early hematopoietic precursor cells are transduced by MDR-1 retroviral vector in mouse gene therapy model. Cancer Gene Ther 1994; 1: 21–5.PubMedGoogle Scholar
  123. 122.
    Sorrentino B, Brandt S, Bodine D, Gottesman M, Pastan I, Cline A, et al. Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1. Science 1992; 257: 99–103.PubMedCrossRefGoogle Scholar
  124. 123.
    Orkin SH, Motulsky AG: Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy. Google Scholar
  125. 124.
    Sterman DH, Treat J, Elshami AA, et al. A phase I clinical trial of adenoviral-mediated herpes simplex virus thymidine kinase gene therapy for malignant mesothelioma. Preliminary Results, in Gene Therapy for Cancer V, San Diego, CA, 1996 P29 (abstr).Google Scholar
  126. 125.
    Yang Y, Nunes FA, Berencsi K, et al. Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 1994; 91: 4407–4411.PubMedCrossRefGoogle Scholar
  127. 126.
    Yang Y, Li Q, Ertl HC, et al. Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 1995; 69: 2004–2015.PubMedGoogle Scholar
  128. 127.
    Goodman JC, Trask TW, Chen SH, et al. Adenoviral-mediated thymidine kinase gene transfer into the primate brain followed by systemic ganciclovir: Pathologic, radiologic, and molecular studies. Human Gene Therapy 1996; 7: 1241–1250.PubMedCrossRefGoogle Scholar
  129. 128.
    Yee D, McGuire Se, Brunner N et al. Adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase in an ascites model of human breast cancer. Human Gene Therapy 1996; 7: 1251–1257.Google Scholar
  130. 129.
    Brand K, Arnold W, Bartels T, et al. Liver-associated toxicity of the HSV-tk/GCV approach and adenoviral vectors. Cancer Gene Therapy 1997; 4: 9–16.PubMedGoogle Scholar
  131. 130.
    Ojeifo JO, Forough R, Paik S, et al. Angiogensis-directed implantation of genetically modified endothelial cells in mice. Cancer Res 1995; 55: 2240–2244.PubMedGoogle Scholar
  132. 131.
    Rancourt C, Robertson MW, Wang M, et al. Endothelial cell vehicles for delivery of cytotoxic genes as a gene therapy approach for carcinoma of the ovary. Clin Cancer Res 1998; 4: 265–270.PubMedGoogle Scholar
  133. 132.
    Vanderkwaak T, Wang M, Gomez-Navarro J, et al: An advanced generation of adenoviral vectors selectively enhances gene transfer for ovarian cancer gene therapy approaches. Gynecol Oncol 1999; 74: 227.PubMedCrossRefGoogle Scholar
  134. 133.
    Rancourt C, Curiel DT: Conditionally replicative adenoviruses for cancer therapy. Advanced Drug Delivery Rev 1997; 27: 67–81.CrossRefGoogle Scholar
  135. 134.
    Bischoff JR, Kim DH, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996; 274: 373–376.PubMedCrossRefGoogle Scholar
  136. 135.
    Rancourt C, Piche A, Gomez-Navarro J, et al. Interleukin-6 modulated conditionally replicative adenovirus as an antitumor/cytotoxic agent for cancer therapy. Clinical Cancer Research 1999; 5: 43–50.PubMedGoogle Scholar
  137. 136.
    Bilbao G, Feng M, Rancourt C, et al. Adenoviral/retroviral vector chimeras-A novel strategy to achieve high efficiency stable transduction in vivo. FASEB J 1997; 11: 624634.Google Scholar
  138. 137.
    Miyoshi H, Takahashi M, Gage F, Verma I. Stable and efficient gene tranfer into the retina using an HIV based lentiviral vector. Proc Natl Acad Sci USA 1997; 94: 10319.PubMedCrossRefGoogle Scholar
  139. 138.
    Bueler H. Adeno-associated viral vectors for gene transfer and gene therapy. Biol Chem 1999; 380: 613.PubMedCrossRefGoogle Scholar
  140. 139.
    Bartlett J, Kleinschmidt J, Boucher R, Samulski R. Targeted adeno-associated virus vector transduction of nonpermissive cells mediated by a bispecific F(ab’ gamma)2 antibody. Nature Biotech 1999; 17: 181.CrossRefGoogle Scholar
  141. 140.
    Yang Q, Mamounas M, Kennedy S, et al. Development of novel cells surface CD34 targeted recombinant adeno-associated virus vectors for gene therapy. Hum Gene Ther 1998; 9: 1929.PubMedCrossRefGoogle Scholar
  142. 141.
    Li S, Huang L. Nonviral gene therapy: Promises and challenges. Gene Therapy 2000; 7: 31.PubMedCrossRefGoogle Scholar
  143. 142.
    Roy K, Mao H, Huang S, Leong K. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med 1999; 5: 387PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Warner K. Huh
    • 1
  • Mack N. Barnes
    • 1
  • F. Joseph Kelly
    • 1
  • Ronald D. Alvarez
    • 1
  1. 1.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyUniversity of Alabama at BirminghamBirminghamUSA

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