Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

A role for intracellular immunization in chemosensitization of tumor cells?

Abstract

Acquired drug resistance represents a major cause of chemotherapy failure in patients with cancer. The characterization of the molecular pathways involved in drug resistance has provided us with new targets to overcome this problem. Many of these target proteins are often overexpressed in human cancers. A number of gene therapy strategies, including antisense oligonucleotides, ribozymes and single-chain antibodies, have been developed to achieve the selective modulation and inhibition of various cellu- lar proteins. Thus, these approaches can be exploited to modulate the resistance phenotype of tumor cells. These gene therapy strategies represent a novel and unique way to enhance the sensitivity of tumor cells to chemotherapeutic drugs. This review will focus on the use of intracellular immunization as a means to modulate the expression of specific genetic determinants involved in the drug resistance phenotype.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Godwin AK et al. High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis Proc Natl Acad Sci USA 1992 89: 3070–3074

    Article  CAS  PubMed  Google Scholar 

  2. Scanlon KJ et al. Molecular basis of cisplatin resistance in human carcinomas: model systems and patients Anticancer Res 1989 9: 1311–1312

    Google Scholar 

  3. Andrews PA, Howell SB . Cellular pharmocology of cisplatin: perspectives on mechanisms of acquired resistance Cancer Cells 1990 2: 35–43

    CAS  PubMed  Google Scholar 

  4. Minagawa Y et al. Enhanced topoisomerase I activity and increased topoisomerase II content in displatin-resitant cancer cell lines Jpn J Cancer Res 1997 88: 1218–1223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Drlica K, Franco RJ . Inhibitors of DNA topoisomerases Biochemistry 1988 27: 2253–2259

    Article  CAS  PubMed  Google Scholar 

  6. Goldstein LJ et al. Expression of a multidrug resistance gene in human cancers J Natl Cancer Inst 1989 81: 116–124

    Article  CAS  PubMed  Google Scholar 

  7. Fojo A, Hamilton TC, Young RC, Ozols RF . Multidrug resistance in ovarian cancer Cancer 1987 60 (Suppl.8): 2075–2080

    Article  Google Scholar 

  8. Chan HS et al. A sensitive method for immunocytochemical detection of P-glycoprotein in multidrug-resistant human ovarian carcinoma cell lines Lab Invest 1989 59: 870–875

    Google Scholar 

  9. Chan HS et al. P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma New Engl J Med 1991 325: 1608–1614

    Article  CAS  PubMed  Google Scholar 

  10. Pirker R et al. MDR1 gene expression and treatment outcome in acute myeloid leukemia J Natl Cancer Inst 1991 83: 708–712

    Article  CAS  PubMed  Google Scholar 

  11. Marie JP, Zittoun R, Sikic BI . Multidrug resitance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity Blood 1991 78: 586–592

    CAS  PubMed  Google Scholar 

  12. Campos L et al. Clinical significance of multidrug resistance P-glycoprotein expression on acute non-lymphagocytic leukemia cells at diagnosis Blood 1992 79: 473–476

    CAS  PubMed  Google Scholar 

  13. Holzmayer TA, Hilsenbeck S, Von Hoff DD, Roninson IB . Clinical correlates of MDR1 P-glycoprotein gene expression in ovarian and small-cell lung carcinomas J Natl Cancer Inst 1992 84: 1486–1491

    Article  CAS  PubMed  Google Scholar 

  14. Goasguen JE et al. Expression of the multidrug resistance-associated P-glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications Blood 1993 81: 2394–2398

    CAS  PubMed  Google Scholar 

  15. Fisher DE . Apoptosis in cancer therapy Cell 1994 78: 539–542

    Article  CAS  PubMed  Google Scholar 

  16. Reed JC . Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance Curr Opin Oncol 1995 7: 541–546

    Article  CAS  PubMed  Google Scholar 

  17. Reed JC . Bcl-2: prevention of apoptosis as a mechanism of drug resistance Hematol/Oncol Clin North Am 1995 9: 451–473

    Article  CAS  Google Scholar 

  18. Eliopoulos AG et al. The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2 Oncogene 1995 11: 1217–1228

    CAS  PubMed  Google Scholar 

  19. Reed JC . Double identity for proteins of the Bcl-2 family Nature 1997 387: 773–776

    Article  CAS  PubMed  Google Scholar 

  20. Nguyen DM et al. Gene therapy for lung cancer: enhancement of tumor suppression by a combination of sequential systemic cisplatin and adenovirus-mediated p53 gene transfer J Thorac Cardiovasc Surg 1996 112: 1372–1377

    Article  CAS  PubMed  Google Scholar 

  21. Pirollo KF et al. P53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy Oncogene 1997 14: 1735–1746

    Article  CAS  PubMed  Google Scholar 

  22. Chang F, Syrjanem S, Syrjanem K . Implications of the p53 tumor-suppressor gene in clinical oncology J Clin Oncol 1995 13: 1009–1022

    Article  CAS  PubMed  Google Scholar 

  23. Warenius HM, Seabra LA, Maw P . Sensitivity to cis-diamminedichloroplatinum in human cancer cells is related to expression of cyclin D1 but no c-Raf-1 protein Int J Cancer 1996 67: 224–231

    Article  CAS  PubMed  Google Scholar 

  24. Hochhauser D et al. Effect of cyclin D1 overexpression on drug sensitivity in human fibrosacrcoma cell line J Natl Cancer Inst 1996 88: 1269–1275

    Article  CAS  PubMed  Google Scholar 

  25. Baserga R . Oncogenes and the strategy of growth factors Cell 1994 79: 927–930

    Article  CAS  PubMed  Google Scholar 

  26. Meyn RE, Stephens LC, Milas L . Programmed cell death and radioresistance Cancer Metast Rev 1996 15: 119–131

    Article  CAS  Google Scholar 

  27. Dickstein B et al. Increased epidermal growth factor receptor in an estrogen-responsive, adriamycin-resistant MCF-7 cell line J Cell Physiol 1993 157: 110–118

    Article  CAS  PubMed  Google Scholar 

  28. Vicker PJ, Dickson RB, Shoemaker R, Cowan KH . A multidrug-resistant MCF-7 human breast cancer cell line which exhibits cross-resistance to antiestrogens and hormone-independent tumor growth in vivo Mol Endocrinol 1988 2: 886–892

    Article  Google Scholar 

  29. Gusterson BA et al. Prognostic importance of c-erbB-2 expression in breast cancer J Clin Oncol 1992 10: 1049–1056

    Article  CAS  PubMed  Google Scholar 

  30. Bergmann C, Hung M, Weinberg R . The neu oncogene encodes an epidermal growth factor receptor related protein Nature 1986 319: 226–229

    Article  Google Scholar 

  31. Berchuck A et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer Cancer Res 1990 50: 4087–4091

    CAS  PubMed  Google Scholar 

  32. Felip E et al. Overexpression of c-erbB-2 in epithelial ovarian cancer, prognostic value and relationship with response to chemotherapy Cancer 1995 75: 2147–2152

    Article  CAS  PubMed  Google Scholar 

  33. Tsai CM et al. Enhanced chemoresistance by elevation of p185neu levels in HER/neu-transfected human lung cancer cells J Natl Cancer Inst 1995 87: 682–684

    Article  CAS  PubMed  Google Scholar 

  34. Tsai CM, Chang KT, Perng RP . Correlation of intrinsic chemoresistance of non-small cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations J Natl Cancer Inst 1993 85: 897–901

    Article  CAS  PubMed  Google Scholar 

  35. Baltimore D . Gene therapy: intracellular immunization Nature 1988 335: 395–396

    Article  CAS  PubMed  Google Scholar 

  36. Aslaro FK, McDonnell WM . Antisense-oligonucleotide therapy New Engl J Med 1995 334: 316–318

    Google Scholar 

  37. James HA, Gibson I . The therapeutic potential of ribozymes Blood 1997 91: 371–382

    Google Scholar 

  38. Marasco W . Intrabodies: turning the humoral immune system outside in for intracellular immunization Gene Therapy 1997 4: 11–15

    Article  CAS  PubMed  Google Scholar 

  39. Chen S-Y, Marasco WA . Novel genetic immunotoxins and intracellular antibodies for cancer therapy Semin Oncol 1996 23: 148–153

    CAS  PubMed  Google Scholar 

  40. Winter G, Milstein C . Man-made antibodies Nature 1991 349: 293–299

    Article  CAS  PubMed  Google Scholar 

  41. Hoogenboom HR, Marks JD, Griffiths AD, Winter G . Building antibodies form their genes Immunol Rev 1992 130: 41–68

    Article  CAS  PubMed  Google Scholar 

  42. Bergmann C, Hung M, Weinberg R . The neu oncogene encodes an epidermal growth factor receptor related protein Nature 1986 319: 226–229

    Article  Google Scholar 

  43. Berchuck A et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer Cancer Res 1990 50: 4087–4091

    CAS  PubMed  Google Scholar 

  44. Barnes MN et al. Novel gene therapy strategy to accomplish growth factor modulation induces enhanced tumor cell chemosensitivity Clin Cancer Res 1996 2: 1089–1095

    CAS  PubMed  Google Scholar 

  45. Paik S . Clinical significance of erbB-2 (HER-2/neu) protein Cancer Invest 1992 10: 575–579

    Article  CAS  PubMed  Google Scholar 

  46. Hancock MC et al. A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines Cancer Res 1991 51: 4575–4580

    CAS  PubMed  Google Scholar 

  47. Deshane J et al. Intracellular single-chain antibody directed against erbB2 down-regulates cell surface erbB2 and exhibits a selective anti-proliferative effect in erbB2 overexpressing cancer cell lines Gene Therapy 1994 1: 332–337

    CAS  PubMed  Google Scholar 

  48. Deshane J et al. Targeted tumor killing via an intracellular antibody against erbB-2 J Clin Invest 1995 96: 2980–2989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Deshane J et al. Targeted eradication of ovarian cancer mediated by intracellular expression of anti-erbB-2 single-chain antibody Gynecol Oncol 1995 59: 8–14

    Article  CAS  PubMed  Google Scholar 

  50. Deshane J et al. Intracellular antibody directed against erbB-2 mediated targeted tumor cell eradication by inducing apoptosis Cancer Gene Ther 1996 3: 89–98

    CAS  PubMed  Google Scholar 

  51. Graus-Porta D, Beerli RR, Hynes NE . Single-chain antibody-mediated intracellular retention of ErbB-2 impairs Neu differentiation factor and epidermal growth factor signaling Molec Cell Biol 1995 15: 1182–1191

    Article  CAS  PubMed  Google Scholar 

  52. Fantl WJ, Johson DE, Williams LT . Signalling by receptor tyrosine kinases Ann Rev Biochem 1993 62: 453–481

    Article  CAS  PubMed  Google Scholar 

  53. Salomon DS, Brandt R, Ciardello F, Normanno N . Epidermal growth factor-related peptides and their receptors in human malignancies Crit Rev Oncol/Hematol 1995 19: 183–232

    Article  CAS  Google Scholar 

  54. Murphy LC et al. Epidermal growth factor: receptor and ligand expression in human breast cancer Semin Cancer Biol 1990 1: 305–315

    CAS  PubMed  Google Scholar 

  55. Murray PA et al. The prognostic significance of transforming growth factors in human breast cancer Br J Cancer 1993 67: 1408–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Aboud-Pirak E et al. Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice J Natl Cancer Inst 1988 80: 1605–1611

    Article  CAS  PubMed  Google Scholar 

  57. Fan Z, Baselga J, Massui H, Mendelsohn J . Antitumor effect of antiepidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografs Cancer Res 1993 53: 4637–4642

    CAS  PubMed  Google Scholar 

  58. Baselga J et al. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies J Natl Cancer Inst 1993 85: 1327–1333

    Article  CAS  PubMed  Google Scholar 

  59. Peng D et al. Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27 and induces G1 arrest in prostatic cancer cell line DU145 Cancer Res 1996 56: 3666–3669

    CAS  PubMed  Google Scholar 

  60. Jannot CB et al. Intracellular expression of a single-chain antibody directed to the EGFR leads to growth inhibition of tumor cells Oncogene 1996 13: 275–282

    CAS  PubMed  Google Scholar 

  61. Beerli RR, Wels W, Hynes NE . Autocrine inhibition of the epidermal growth factor receptor by intracellular expression of a single-chain antibody Biochem Biophy Res Commun 1994 204: 666–672

    Article  CAS  Google Scholar 

  62. Krajewski S et al. Analysis of Bax and Bcl-2 expression in p53-immunopositive breast cancers Clin Cancer Res 1997 3: 199–208

    CAS  PubMed  Google Scholar 

  63. Doglioni C et al. The prevalence of Bcl-2 immunoreactivity in breast carcinomas and its clinicopathological correlates with particular reference to estrogen receptor status Virchows Arch 1994 424: 47–51

    Article  CAS  PubMed  Google Scholar 

  64. Nakasu S et al. bcl-2 protein expression in tumors of the central nervous system Acta Neuropathol 1994 88: 520–526

    Article  CAS  PubMed  Google Scholar 

  65. Alderson LM et al. Human gliomas with wild-type p53 express bcl-2 Cancer Res 1995 55: 999–1001

    CAS  PubMed  Google Scholar 

  66. Bronner MP, Culin C, Reed JC, Furth EE . The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model Am J Pathol 1995 146: 20–26

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Xerri L et al. Predominant expression of the long isoform of Bcl-X in human lymphomas Br J Haematol 1996 92: 900–907

    Article  CAS  PubMed  Google Scholar 

  68. Sclaifer D et al. High expression of the Bcl-X gene in Reed–Sternberg cells of Hodgkin’s disease Blood 1995 85: 2671–2677

    Google Scholar 

  69. Krajewski M et al. Elevated expression of Bcl-X and reduced BAK in primary colorectal carcinoma Cancer Res 1996 56: 2422–2429

    PubMed  Google Scholar 

  70. Krajewski M et al. Immunohistochemical analysis of Bcl-2, BAX, Bcl-X and MCL-1 expression in prostate cancers Am J Pathol 1996 148: 1567–1575

    PubMed  PubMed Central  Google Scholar 

  71. Krajewski S et al. Immunohistochemical analysis of Bcl-2, Bcl-X, MCL-1 and BAX in tumors of central and peripheral nervous system origin Am J Pathol 1997 150: 805–814

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Tu Y et al. Bcl-x expression in multiple myeloma: possible indicator of chemoresistance Cancer Res 1998 58: 256–262

    CAS  PubMed  Google Scholar 

  73. Grim JE et al. A family of plasmid vectors for the intracellular expression of single-chain antibodies Gene (Submitted)

  74. Piché A et al. Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7 Cancer Res 1998 58: 2134–2140

    PubMed  Google Scholar 

  75. Piché A et al. Modulation of drug-induced apoptosis by anti-Bcl-2 single-chain antibodyin ovarian cancer cells Tumor Targeting 1998 3: 147–155

    Google Scholar 

  76. Bos JL . Ras oncogenes in human cancer: a review Cancer Res 1989 49: 4682–4689

    CAS  PubMed  Google Scholar 

  77. Mills NE et al. Increased prevalence of K-ras oncogene mutations in lung adenocarcinomas Cancer Res 1995 55: 1444–1447

    CAS  PubMed  Google Scholar 

  78. Werge TM, Biocca S, Cattaneo A . Cloning and intracellular expression of a monoclonal antibody to the p21ras protein FEBS Lett 1990 274: 193–198

    Article  CAS  PubMed  Google Scholar 

  79. Cochet O et al. Intracellular expression of an antibody fragment-neutralizing p21 Ras promotes tumor regression Cancer Res 1998 58: 1170–1176

    CAS  PubMed  Google Scholar 

  80. Nooter K et al. Constitutive expression of the c-Ha-ras oncogene inhibits doxorubicin-induced apoptosis and promotes cell survival in a rhabdomyosarcome cell line Br J Cancer 1995 71: 556–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hartmann A, Blaszyk H, Kovach JS, Sommer SS . The molecular epidemiology of p53 gene mutations in human breast cancer Trends Genet 1997 13: 27–33

    Article  CAS  PubMed  Google Scholar 

  82. Hoedemaeker FJ et al. A single chain Fv fragment of P-glycoprotein-specific monoclonal antibody C219 J Biol Chem 1997 47: 29784–29789

    Article  Google Scholar 

  83. Pines J . Protein kinases and cell cycle control Semin Cell Biol 1994 5: 399–408

    Article  CAS  PubMed  Google Scholar 

  84. Motokura T, Arnold A . Cyclins and oncogenesis Biochem Biophys Acta 1993 1155: 63–78

    CAS  PubMed  Google Scholar 

  85. Hall M, Peters G . Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer Adv Cancer Res 1996 68: 67–108

    Article  CAS  PubMed  Google Scholar 

  86. Arnold A et al. Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma J Clin Invest 1989 83: 2034–2040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Bellacosa A et al. Cyclin D1 gene amplification in human laryngeal squamous cell carcinomas: prognostic significance and clinical implications Clin Cancer Res 1996 2: 175–180

    CAS  PubMed  Google Scholar 

  88. Poul M-A, Teyssier C, Lefranc M-P . Inhibition of cyclin D1 oncogene with intracellular single chain antibodies. Exploring and exploiting antibody and Ig superfamily combining sites Keystone Symposia, New Mexico, 22–28 February 1996

    Google Scholar 

  89. Wu L, Wu A, Jiang K . Effect of antisense c-erbB2 on biologic behaviour and chemotherapeutic drug sensitivity in human ovarian cancer cells Chung Hua Fu Can Ko Tsa Chih 1996 31: 169–172

    Google Scholar 

  90. Brader KR, Wolf JK, Chakrabarty S, Price JE . Epidermal growth factor receptor (EGFR) antisense transfection reduces the expression of EGFR and suppresses the malignant phenotype of a human ovarian cancer cell line Oncol Res 1998 5: 1269–1274

    CAS  Google Scholar 

  91. Grandis JR et al. Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells Oncogene 1997 15: 409–416

    Article  CAS  Google Scholar 

  92. He YK et al. Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter J Natl Cancer Inst 1998 90: 1080–1087

    Article  CAS  PubMed  Google Scholar 

  93. Dixit M et al. Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA J Natl Cancer Inst 1997 89: 365–373

    Article  CAS  PubMed  Google Scholar 

  94. Kornmann M, Arber N, Korc M . Inhibition of basal and mitogen-stimulated pancreatic cancer cell growth by cyclin D1 antisense is associated with loss of tumorigenicity and potentiation of cytotoxicity to cisplatinum J Clin Invest 1998 101: 344–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Driscoll B et al. Cyclin D-1 antisense RNA destablilizes PRB and retards lung cancer cell growth Am J Physiol-Lung Cell & Mol Physiol 1997 17: 941–949

    Article  Google Scholar 

  96. Zhou P et al. Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of eosphagal cancer cells Oncogene 1995 11: 571–580

    CAS  PubMed  Google Scholar 

  97. Arber N et al. Antisense to cyclin D1 inhibits the growth and tumorigenicity of human colon cancer cells Cancer Res 1997 57: 1569–1574

    CAS  PubMed  Google Scholar 

  98. Keith FJ, Bardbury DA, Ahu YM, Russell NH . Inhibition of bcl-2 with antisense oligonucleotides induces apoptosis and increases the sensitivity of AML blasts to Ara-C Leukemia 1995 9: 131–138

    CAS  PubMed  Google Scholar 

  99. Jansen B et al. Bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice Nature Med 1998 4: 232–234

    Article  CAS  PubMed  Google Scholar 

  100. Arteaga CL, Holt JT . Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice Cancer Res 1996 56: 1098–1103

    CAS  PubMed  Google Scholar 

  101. Aoki K, Yoshida T, Sugimura T, Terada M . Liposme-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity Cancer Res 1995 55: 3810–3816

    CAS  PubMed  Google Scholar 

  102. Holt JT, Arteaga CL, Roberston D, Moses HL . Gene therapy for the treatment of metastatic breast cancer by in vivo transduction with breast-targeted retroviral vector expressing antisense c-fos RNA Hum Gene Ther 1996 7: 1367–1380

    Article  CAS  PubMed  Google Scholar 

  103. Bunnell BA, Morgan RA . Gene Therapy for AIDS Mol Cell 1996 1: 1–12

    Google Scholar 

  104. Kobayashi H, Dorai T, Hooland JF, Ohnuma T . Reversal of drug sensitivity in multidrug-resistant tumor cells by an MDR1 (PGY1) ribozyme Cancer Res 1994 54: 1271–1275

    CAS  PubMed  Google Scholar 

  105. Kiehntopf M et al. Ribozyme-mediated cleavage of the MDR-1 transcript restores chemosensitivity in previously resistant cancer cells EMBO J 1994 13: 4645–4646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Dorai T, Olsson CA, Katz AE, Buttyan R . Development of a hammerhead ribozyme against bcl-2. I. Preliminary evaluation of a potential gene therapeutic agent for hormone-refractory human prostate cancer Prostate 1997 32: 246–258

    Article  CAS  PubMed  Google Scholar 

  107. Dorai T, Goluboff ET, Olsson CA, Buttyan R . Development of a hammerhead ribozyme against Bcl-2. 2. Ribozyme treatment sensitizes hormone-resistant prostate cancer cells to apoptotic agents Anticancer Res 1997 17: 3307–3312

    CAS  PubMed  Google Scholar 

  108. Rancourt C et al. Basic fibroblast growth factor enhancement of adenovirus-mediated delivery of the herpes simple virus thymidine kinase gene results in augmented therapeutic benefit in a murine model of ovarian cancer Clin Cancer Res 1998 4: 2455–2461

    CAS  PubMed  Google Scholar 

  109. Gu D et al. Retargeting adenovirus vectors with FGF-2 leads to enhanced efficacy and decreased toxicity Proc Am Assoc Cancer Res 1998 39: 512

    Google Scholar 

  110. Feng M et al. Stable in vivo gene transduction via a novel adenoviral/retroviral chimeric vector Nature Biotechnol 1997 15: 866–870

    Article  CAS  Google Scholar 

  111. Johnston KM et al. HSV/AAV hybrid amplicon vectors extend transgene expression in human glioma cells Hum Gene Ther 1997 8: 359–370

    Article  CAS  PubMed  Google Scholar 

  112. Roth JA, Cristiano RJ . Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 1997 89: 21–39

    Article  CAS  PubMed  Google Scholar 

  113. Bi WL, Parysek LM, Warnick R, Stambrook PJ . In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSVtk retroviral gene therapy Hum Gene Ther 1993 4: 725–731

    Article  CAS  PubMed  Google Scholar 

  114. Chen CY et al. Effect of herpes simplex thymidine kinase expression levels on ganciclovir-mediated cytotoxicity and the ‘bystander effect’ Hum Gene Ther 1995 6: 1467–1476

    Article  CAS  PubMed  Google Scholar 

  115. Hamel W, Magnelli L, Chiarugi VP, Israel MA . Herpes simplex virus thymidine kinase/ganciclovir-mediated apoptotic death of bystander cells Cancer Res 1996 56: 2697–2702

    CAS  PubMed  Google Scholar 

  116. Fujiwara T et al. Therapeutic effect of a retroviral wild-type p53 expression vector in an orthoptic lung cancer model J Natl Cancer Inst 1994 86: 1458–1462

    Article  CAS  PubMed  Google Scholar 

  117. Pirollo KF et al. p53-mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy Oncogene 1997 14: 1735–1746

    Article  CAS  PubMed  Google Scholar 

  118. Frank DK, Frederick MJ, Liu T-J, Clayman GL . Bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of human squamous cell carcinoma of the head and neck Clin Cancer Res 1998 4: 2521–2527

    CAS  PubMed  Google Scholar 

  119. Sullivan GF, Amenta PS, Villanueva JD, Alvarez CJ . The expression of drug resistance gene products during the progression of human prostate cancer Clin Cancer Res 1998 4: 1393–1403

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a grant from the Medical Research Council of Canada MT-15018, and by an institutional grant from Université de Sherbrooke.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Piché, A., Rancourt, C. A role for intracellular immunization in chemosensitization of tumor cells?. Gene Ther 6, 1202–1209 (1999). https://doi.org/10.1038/sj.gt.3300952

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3300952

Keywords

This article is cited by

Search

Quick links