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Thymidine Kinases

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Gene Therapy

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Abstract

The principal objective of gene transfer therapy in cancer patients, as it is with chemo- or radiotherapy, is to kill the target (tumor) cells. This contrasts with the gene therapy of most other diseases in which the aim is both to preserve the target cells and to correct the underlying genetic defects which are responsible for the relevant pathology [1]. Although efforts directed at classical genetic correction of cancer cells, using tumor suppressor gene replacement or antisense strategies, have shown some encouraging results in animal models [2, 3], even these ultimately seek to promote cell death, for example by the induction of apoptosis [4].

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References

  1. Anderson, W. E (1992) Hum. Gene Ther. Science 256: 808–813.

    CAS  Google Scholar 

  2. Fujiwara, T., Grimm, E. A. and Roth, J. A. (1994) Gene Therapeutics and Gene Therapy for Cancer. Curr. Opin. Oncol. 6: 96–105.

    Article  PubMed  CAS  Google Scholar 

  3. Mercola, D. and Cohen, J. S. (1995) Antisense approaches to cancer gene therapy. Cancer Gene Therapy 2: 47–59.

    PubMed  CAS  Google Scholar 

  4. Liu, T. -J. et al. (1995) Apoptosis Induction Mediated by Wild-Type p53 Adenoviral Gene Transfer in Squamous Cell Carcinoma of the Head and Neck’. Cancer Res. 55: 3117–3122.

    PubMed  CAS  Google Scholar 

  5. Vile, R. G. and Russell, S. J. (1994) Gene transfer technologies for the gene therapy of cancer. Gene Therapy 1: 88–98.

    PubMed  CAS  Google Scholar 

  6. Pardoll, D. M. (1995) Paracrine Cytokine Adjuvants in Cancer Immunotherapy. Annu. Rev. Immunol. 13: 399–415.

    Article  PubMed  CAS  Google Scholar 

  7. Moolten, F. L. (1994) Drug sensitivity (“suicide”) genes for selective cancer chemotherapy. Cancer Gene Ther. 1: 279–287.

    PubMed  CAS  Google Scholar 

  8. Wagner, M. J., Sharp, J. A. and Summers, W. C. (1981) Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1. Proc. Natl. Acad. Sci. USA 78: 1441–1445.

    Article  PubMed  CAS  Google Scholar 

  9. Elion, G. B. The biochemistry and mechanism of action of acyclovir. Antimicrob. Chemother. 12: 9–17 (1983)

    CAS  Google Scholar 

  10. Nishiyama, Y. and Rapp, E (1979) Anticellular efects of 9-(2-hydroxyethoxymethl) gguanine against herpes simplex virus-transformed cells. Gen. Virol. 45: 227–230.

    Article  CAS  Google Scholar 

  11. Balzarini, J., De Clercq, E., Verbruggen, A., Ayusawa, D. and Seno, T. (1985) Highly selective cytostatic activity of (E)-5-(2-bromovinyl)-2’-deoxxyuridine derivatives for murine mammary carcinoma (FM3A) cells transformed with the herpes simplex virus type 1 thymidine kinase gene. Mol. Pharmacol. 28: 581–587.

    PubMed  CAS  Google Scholar 

  12. Huber, B. E., Richards, C. A. and Krenitsky, T. A. (1991) Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: An innovative approach for cancer therapy. Proc. Natl. Acad. Sci. USA 88: 8039–8043.

    Article  PubMed  CAS  Google Scholar 

  13. Reid, R., Eng-Chung, M., Eng-Shang, H. and Topal, M. D. (1988) Insertion and extension of acyclic, dideoxy, and ara nucleotides by herpesvirdae, human alpha and human beta polymerases. J. Biol. Chem. 263: 3898–3904.

    PubMed  CAS  Google Scholar 

  14. Freeman, S. M. et al. (1993) The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res. 53: 5274–5283.

    PubMed  CAS  Google Scholar 

  15. Samejima, Y. and Meruelo, D. (1995) `Bystander killing’ induces apoptosis and is inhibited by forskolin. Gene Ther. 2: 50–58.

    Google Scholar 

  16. Wyllie, A. H. (1993) Apoptosis (The 1992 Frank Rose Memorial Lecture). Brit. J. Cancer 67: 205–208.

    Article  PubMed  CAS  Google Scholar 

  17. Stewart, B. W. (1994) Mechanisms of Apoptosis: Integration of Genetic, Biochemical, and Cellular Indicators. J. Nat. Cancer Inst. 86: 1287–1293.

    Google Scholar 

  18. Kaneko, Y. and A., T. (1995) Gene therapy of hepatoma: bystander effects and non-apoptotic cell death induced by thymidine kinase and ganciclovir. Cancer Lett. 96: 105–110.

    Article  PubMed  CAS  Google Scholar 

  19. Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A. and Jacks, T. (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362: 847–849.

    Google Scholar 

  20. Fisher, D. E. (1994) Apoptosis in Cancer Therapy: Crossing the Threshold. Cell 78: 539–542.

    Article  PubMed  CAS  Google Scholar 

  21. Wigler, E. A. (1977) Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell 11: 223–232.

    Article  PubMed  CAS  Google Scholar 

  22. Moolten, E L. (1986) Tumor chemosensitivity conferred by inserted Herpes thymidine kinase genes: Paradigm for a prospective cancer control strategy. Cancer Res. 46, 5276.

    PubMed  CAS  Google Scholar 

  23. Moolten, E L. and Wells, J. M. (1990) Curability of tumors bearing Herpes Thymidine Kinase genes transferred by retroviral vectors. J. Nat. Cancer Inst. 82: 297–300.

    Article  PubMed  CAS  Google Scholar 

  24. Jolly, D. (1994) Viral vector systems for gene therapy. Cancer Gene Ther. 1: 51–64.

    PubMed  CAS  Google Scholar 

  25. Crystal, R. G. (1995) Transfer of genes to humans: early lessons and obstacles to success. Science 270: 404–410.

    Article  PubMed  CAS  Google Scholar 

  26. Miller, N. and Vile, R. G. (1995) Targeted vectors for gene therapy. FASEB J. 9: 190–199.

    PubMed  CAS  Google Scholar 

  27. Vile, R. G. (1994) Tumor specific gene expression. Seminars in Cancer Biology 5: 429–436.

    PubMed  CAS  Google Scholar 

  28. Vile, R. G. and Hart, I. R. (1993) Use of tissue-specific expression of the Herpes Simplex Virus thymidine kinase gene to inhibit growth of established murine melanomas following direct intratumoral injection of DNA. Cancer Res. 53: 3860–3864.

    PubMed  CAS  Google Scholar 

  29. Vile, R. G., Nelson, J. A., Castleden, S. C., Chong, H. and Hart, I. R. (1994) Systemic gene therapy of murine melanoma using tissue specific expression of the HSVtk gene involves an immune component. Cancer Res. 54: 6228–6234.

    PubMed  CAS  Google Scholar 

  30. Culver, K. W. et al. (1992) In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256: 1550–1552.

    CAS  Google Scholar 

  31. Short, M. P. et al. (1990) Gene delivery to glioma cells in rat brain by grafting of a retro-virus packaging cell line. J. Neurosci. Res. 27: 427–439.

    Article  PubMed  CAS  Google Scholar 

  32. Chen, S. -H., Shine, H. D., Goodman, J. C., Grosman, R. G. (1994) Gene therapy for brain tumors: Regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc. Natl. Acad. Sci. USA 91: 3054–3057.

    Article  CAS  Google Scholar 

  33. Roy Smythe, W. et al. (1994) Use of recombinant adenovirus to transfer the Herpes Simplex Virus thymidine kinase (HSVtk) gene to thoracic neoplasms: an effective in vitro drug sensitisation system. Cancer Res. 54: 2055–2059.

    Google Scholar 

  34. Vile, R. G. and Russell, S. J. (1995) Retroviruses as vectors. Brit. Med. Bull. 51: 12–30.

    PubMed  CAS  Google Scholar 

  35. Bi, W. L., Parysek, L. M., Warnick, R. and Stambrook, P. J. (1993) In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retro-viral gene therapy. Hum. Gene Ther. 4: 725–731.

    CAS  Google Scholar 

  36. Hooper, M. L. and Subak-Sharpe, J. H. (1981) Metabolic cooperation between cells. Int. Rev. Cytol. 69: 45–104.

    Article  PubMed  CAS  Google Scholar 

  37. Pitts, J. D. (1994) Cancer gene therapy: a bystander effect using the gap junctional pathway. Molec. Carcinogen. 11: 127–130.

    Article  CAS  Google Scholar 

  38. Colombo, M. B. et al. (1995) Retroviral transduction of the connexin 43 gene increases the efficacy of `suicide’ gene transfer in malignant gliomas. Gene Ther. 2 Si, 80.

    Google Scholar 

  39. Marini III, F. C., Nelson, J. A. and Lapeyre, J. -N. (1995) Assessment of bystander effect potency produced by intratumoral implantation of HSVtk-expressing cells using surrogate marker secretion to monitor tumor growth kinetics. Gene Ther. 2: 655–659.

    CAS  Google Scholar 

  40. Smythe, W. R., Hwang, H. C. and Amin, K. J. et al. (1994) Use of recombinant adenovirus to transfer the herpes simplex virus thymidine kinase (HSV-tk) gene to thoracic neoplasms: an effective in vitro drug sensitization system. Cancer Res. 54: 2055–2059.

    PubMed  CAS  Google Scholar 

  41. Ram, Z., Culver, K. W., Walbridge, S., Blaese, R. M. and Oldfield, E. H. (1993) In situ retroviral mediated gene transfer for the treatment of brain tumors in rats. Cancer Res. 53: 83–88.

    CAS  Google Scholar 

  42. Ram, Z. et al. (1993) Toxicity studies of retroviral-mediated gene transfer for the treatment of brain tumors. J. Neurosurg. 79: 400–407.

    Article  PubMed  CAS  Google Scholar 

  43. Tapscott, S. J., Miller, A. D., Olson, J. M. and Berger, M. S. (1994) Gene therapy of rat 9L gliosarcoma tumors by transduction with slectable genes does not require drug selection. Proc. Natl. Acad. Sci. USA 91: 8185–8189.

    Article  PubMed  CAS  Google Scholar 

  44. Culver, K. W. and Blaese, R. M. (1994) Gene therapy for cancer. Trends Genet. 10: 174–178.

    Article  PubMed  CAS  Google Scholar 

  45. Oldfield, E. H. et al. (1993) Clinical Protocol: Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum. Gene Ther. 4: 39–69.

    Article  PubMed  CAS  Google Scholar 

  46. Ram, Z. e. a. (1995) Summary of results and conclusions of the Gene Ther. apy of malignant brain tumors: clincal study. J. Neurosurg 82, 343A.

    Google Scholar 

  47. Chen, S. H. et al. (1995) Combination gene therapy for liver metastasis of colon carcinoma in vivo. Proc. Natl. Acad. Sci. USA 92: 2577–2581.

    Article  CAS  Google Scholar 

  48. Hurford, J. R. K., Dranoff, G., Mulligan, R. C. and Tepper, R. I. (1995) Gene therapy of metastatic cancer by in vivo retroviral gene targeting. Nat. Genet. 10: 430–435.

    Article  PubMed  CAS  Google Scholar 

  49. Freeman, S. M., McCune, C., Angel, C., Abraham, G. N. and Abboud, C. N. (1992) Treatment of ovarian cancer using HSV-TK gene modified vaccine-regulatory issues. Hum. Gene Ther. 3: 342–349.

    Google Scholar 

  50. Whartenby, K. A., Abboud, C. N., Marrogi, A. J., Ramesh, R. and Freeman, S. M. The biology of cancer gene therapy. Lab. Investig. 72, 131–145 (1995)

    PubMed  CAS  Google Scholar 

  51. Freeman, S. M., Ramesh, R., Marrogi, A. J., Jensen, A. and Abboud, C. N. (1994) In vivo studies on the mechanism of the bystander effect. Cancer Gene Ther. 1, 326.

    Google Scholar 

  52. Nabel, G. J. et al. (1992) Clinical Protocol: Immunotherapy of malignancy by in vivo gene transfer into tumors. Hum. Gene Ther. 3: 399–410.

    Article  Google Scholar 

  53. Caruso, M. et al. (1993) Regression of established macroscopic liver metastases after in situ transduction of a suicide gene. Proc. Natl. Acad. Sci. USA 90: 7024–7028.

    Article  PubMed  CAS  Google Scholar 

  54. Barba, D., Hardin, J., Sadelain, M. and Gage, F. H. (1994) Development of anti tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc. Natl. Acad. Sci. USA 91: 4348–4352.

    Article  PubMed  CAS  Google Scholar 

  55. 55. Vile, R. G., Chong, H. C. and Dorudi, S. (1996) Immunosurveillance of cancer: specific and non-specific mechanisms. In:Dalgleish, A. G., Browning, M. J. (eds), Tumor Immunology. Cambridge University Press, pp. 7–38; in press.

    Google Scholar 

  56. Mullen, C. A., Coale, M. M., Lowe, R. and Blaese, R. M. (1994) Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor. Cancer Res. 54: 1503–1506.

    PubMed  CAS  Google Scholar 

  57. Consalvo, M. et al. (1995) 5-fluorocytosine-induced eradication of murine adenocarcinomas engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory. J. Immunol. 154: 5302–5312.

    Google Scholar 

  58. Cavallo, E. et al. (1992) Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to non immunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene transfer. J. Immunol. 149: 3627–3635.

    PubMed  CAS  Google Scholar 

  59. Colombo, M. P. and Forni, G. (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol. Today 15: 48–51.

    Article  PubMed  CAS  Google Scholar 

  60. Dranoff, G. et al. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte macrophage colony stimulating factor stimulates potent, specific, and long lasting anti-tumor immunity. Proc. Natl. Acad. Sci. USA 90: 3539–3543.

    Article  PubMed  CAS  Google Scholar 

  61. Huang, A. Y. C. et al. (1994) Role of bone marrow derived cells in presenting MHC Class I-restricted tumor antigens. Science 264: 961–965.

    Article  PubMed  CAS  Google Scholar 

  62. Raychaudhuri, S. and Morrow, W. J. W. (1993) Can soluble antigens induce CD8+ cytotoxic T cell responses? A paradox revisited. Immunol. Today 14: 344–348.

    Article  PubMed  CAS  Google Scholar 

  63. Udono, H., Levey, D. L. and Srivastava, P. K. (1994) Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8+ T cells in vivo. Proc. Natl. Acad. Sci. USA 91: 3077–3081.

    Article  CAS  Google Scholar 

  64. Hellstrom, K. E., Hellstrom, I. and Chen, L. (1995) Can co-stimulated tumor immunity be therapeutically efficacious? Immunol. Rev. 145: 123–145.

    Article  PubMed  CAS  Google Scholar 

  65. Pardoll, D. M. Cancer vaccines. Immunol. Today 14, 310–316. (1993)

    Article  PubMed  CAS  Google Scholar 

  66. Grabbe, S., Beissert, S., Schwarz, T. and Granstein, R. D. (1995) Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy? Immunol. Today 16: 117–121.

    Article  PubMed  CAS  Google Scholar 

  67. Golumbek, P. T. et al. (1992) Herpes simplex-1 virus thyumidine kinase gene is unable to completely eliminate live, nonimmunogenic tumor cell vaccines. J. Immunother. 12: 224–230.

    Article  PubMed  CAS  Google Scholar 

  68. Moolten, F., Wells, J. M. and P. J., M. (1992) Multiple transuction as a means of preserving ganciclovir chemosensitivity in sarcoma cells carrying retrovirally transduced herpes thymidine kinase genes. Cancer Lett. 64: 257–263.

    Article  PubMed  CAS  Google Scholar 

  69. Moolten, E L., Wells, J. M., Heyman, R. A. and Evans, R. M. (1990) Lymphoma regression induced by ganciclovir in mice bearing a herpes thymidine kinase transgene. Hum. Gene Ther. 1: 125–134.

    Article  PubMed  CAS  Google Scholar 

  70. Cool, V. et al. (1995) The bystander effect associated to HSVtk gene transfer is absent in intracerebral tumors and seems to be mainly immune mediated in subcutaneous tumors. Gene Ther. 2 Si, 84.

    Google Scholar 

  71. Chong, H. c., Castleden, S., Diaz, R. M., Hart, I. R. and Vile, R. G. (1995) Combination Gene Therapies for the immunotherapy of cancer. Gene Ther. 2 51, 80.

    Google Scholar 

  72. Ram, Z. et al. (1994) In vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors. J. Neurosurg. 80: 535–540.

    CAS  Google Scholar 

  73. Dropulic, B. and Jeang, K. T. (1994) Gene therapy for human immunodeficiency virus infection: genetic antiviral strategies and targets for intervention. Hum. Gene Ther. 5: 927–939.

    Article  PubMed  CAS  Google Scholar 

  74. Guzman, R. J., Hirschowitz, E. A., Brody, S. L., Crystal, R. G., Epstein, S. E. and Finkel, T. (1994) In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene. Proc. Natl. Acad. Sci. USA 91: 10732–10736.

    CAS  Google Scholar 

  75. Ohno, T., Gordon, D., San H., Pompili, V. J., Imperiale, M. J., Nabel, G. J. and Nabel, E. G. (1994) Gene Therapy for Vascular Smooth Muscle Cell proliferation After Arterial Injury. Science 265: 781–784.

    Article  PubMed  CAS  Google Scholar 

  76. Tiberghien, P., Reynolds, C. W. and Keller, J. et al. (1994) Ganciclovir tratment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation. Blood 84: 1333–1341.

    PubMed  CAS  Google Scholar 

  77. Lupton, S. D., Bruton, L. L., Kalberg, V. A. and Overell, R. W. (1991) Dominant positive and negative selection using a hygromcyin phosphotransferase-thymidine kinase fusion gene. Mol. Cell Biol. 11: 3374–3378.

    PubMed  CAS  Google Scholar 

  78. Moolten, F. L. and Cupples, L. A. (1992) A model for predicting the risk of cancer consequent to retroviral gene therapy. Hum. Gene Ther. 3: 479–486.

    Article  PubMed  CAS  Google Scholar 

  79. Moolten, F. L. (1990) Mosaicism produced by gene insertion as a means of improving chemotherapeutic selectivity. Crit. Rev. Immunol. 10: 203–233.

    PubMed  CAS  Google Scholar 

  80. Russell, S. J. (1994) Replicating vectors for cancer therapy: a question of strategy. Sem. Cancer Biol. 5: 437–443.

    CAS  Google Scholar 

  81. Black, M. E. and Loeb, L. A. (1993) Creation of HSV-1 thymidine kinase mutants for gene therapy. Cancer Gene Ther. 1 (Suppl. 1): 2.

    Google Scholar 

  82. Black, M. E. and Loeb, L. A. (1993) Identification of important residues within the putative nucleoside binding site of HSV-1 thymidine kinase by random sequence selection: analysis of selected mutants in vitro. Biochemistry 32: 11618–11626.

    Article  CAS  Google Scholar 

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  1. R. G. Vile
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  1. Max-Delbrück-Centrum für molekulare Medizin, Robert-Rössle-Strasse 10, D-13122, Berlin-Buch, Germany

    Thomas Blankenstein

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© 1999 Birkhäuser Verlag Basel

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Vile, R.G. (1999). Thymidine Kinases. In: Blankenstein, T. (eds) Gene Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7011-5_16

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  • DOI: https://doi.org/10.1007/978-3-0348-7011-5_16

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