Advertisement

Suicide Gene Therapy in Liver Tumors

  • Long R. Jiao
  • Roman Havlik
  • Joanna Nicholls
  • Steen Lindkaer Jensen
  • Nagy A. Habib
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 90)

Abstract

Charaterization of a variety of genomic defects in malignant cells (1) has led to attempts to treat cancer by gene therapy. Gene therapy is a therapeutic approach in which therapeutic nucleic acids are transferred into the affected organs. Although the ideal concept would be the replacement of the abnormal gene by a copy of the functional gene, currently there have not been reliable and safe techniques to allow the site-specific integration of DNA into the human genome (2). Thus, almost all gene therapies are developed by simply transferring the therapeutic gene into somatic cells without replacing the abnormal gene. The goal is to identify and correct genetic abnormalities interfering with the cell cycle and to correct them in all cells. Technically, there are two methods amenable for gene transfer: reintroduction of in vitro transferred gene into the body and direct transfer of gene into the target cells in vivo.

Keywords

Gene Therapy Cystic Fibrosis Transmembrane Conductance Regulator Thymidine Kinase Colorectal Liver Metastasis Bystander Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Bishop, J. M. (1987) The molecular genetics of cancer. Science 235, 305–311.PubMedCrossRefGoogle Scholar
  2. 2.
    Lantsov, V. A. (1994) Ideal gene therapy: approaches and horizons. Mol. Biol. 28, 321–327.Google Scholar
  3. 3.
    Soloman, E., Borrow, J., and Goddard, A. D. (1991) Chromosome aberratons and cancer. Science 254, 1153–1160.CrossRefGoogle Scholar
  4. 4.
    Xu, G. W., Sun, Z. T., Forrester, K., et al. (1996) Tissue-specific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by tetroviral-mediated transfer of the wild-type p53 gene. Hepatology 24, 1264–1268.PubMedCrossRefGoogle Scholar
  5. 5.
    Kanai, F., Shiratori, Y., Yoshida, Y., et al. (1996)Gene therapy for alpha-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus. Hepatology 23, 1359–1367.PubMedGoogle Scholar
  6. 6.
    Kanai, F., Lan, K. H., Shiratori, Y., et al. (1997) In vivo gene therapy for alpha-fetoprotein producing hepatocellular carcinoma by adenovirus-mediated transfer of cytosine deaminase gene. Cancer Res. 57, 461–465.PubMedGoogle Scholar
  7. 7.
    Ukei, T., Nakata, K., and Mawatari, F. (1998) Retro-virus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice. Int. J. Mol. Med. 1, 671–675.Google Scholar
  8. 8.
    Gnant, M. F., Puhlmann, M., Bartlett, D. L., et al. (1999) Regional versus systemic delivery of recombinant vaccinia virus as suicide gene therapy for murine liver metastases. Ann. Surg. 230, 350–360.CrossRefGoogle Scholar
  9. 9.
    Mitry, R. R., Sarraf, C. E., Wu, C. G., et al. (1997) Wild-type p 53 induces apoptosis in Hep 3 B through up-regulation of bax expression. Lab. Invest. 77, 369–378.PubMedGoogle Scholar
  10. 10.
    Habib, N. A., Ding, S. F., El-Masry, R., et al. (1996) Preliminary report: the short-term effects of direct p53 DNA injection in primary hepatocellular carcinomas. Cancer Detect. Prev. 20, 103–107.PubMedGoogle Scholar
  11. 11.
    Habib, N. A., Sarraf, C. E., Mitry, R. R., et al. (2001) E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumours. Hum. Gene Ther. 12, 219–226.PubMedCrossRefGoogle Scholar
  12. 12.
    Crystal, R. G., Hirschowitz, E., Lieberman, M., et al. (1997) Phase I study of direct administration of a replication deficient adenovirus vector containing E. coli cytosine deaminase gene to metastatic colon carcinoma of the liver in association with the oral administration of the pro-drug 5-fluorocytosine. Hum. Gene Ther. 8, 985–1001.PubMedCrossRefGoogle Scholar
  13. 13.
    Sung, M. W., Yeh, H. C., Thung, S. N., et al. (2001) Intratumoral adenovirus-mediated suicide gene transfer for hepatic metastases from colorectal adenocarcinoma∶results of a phase I clinical trial. Mol. Ther. 4, 182–191.PubMedCrossRefGoogle Scholar
  14. 14.
    Hubber, 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.CrossRefGoogle Scholar
  15. 15.
    Moolten, F. L. (1986) Tumour chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 46, 5276–5281.PubMedGoogle Scholar
  16. 16.
    Moolten, F. L. and Wells, J. M. (1990) Curability of tumours bearing herpes thymidine kinase genes transferred by retroviral vectors. J. Natl. Cancer Inst. 82, 297–300.PubMedCrossRefGoogle Scholar
  17. 17.
    Freeman, S., Abboud, C., Whartenby, K. et al. (1993) The “bystander effect”; tumour regression when a fraction of the tumour mass is genetically modified. Cancer Res. 53, 5274–5283.PubMedGoogle Scholar
  18. 18.
    Nakabayashi, H., Watanebe, K., Saito, A., et al. (1989) Transcriptional regulation of alpha-fetoprotein expression by dexamethsone in human hepatoma cells. J. Biol. Chem. 264, 271.Google Scholar
  19. 19.
    Ido A., Nakata K., Kato Y., et al. (1995) Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter. Cancer Res. 55, 3105–3109.PubMedGoogle Scholar
  20. 20.
    Mawatari, F., Tsuruta, S., Ido, A., et al. (1998) Retrovirus-mediated gene therapy for hepa-tocellular carcinoma:selective and enhanced suicide gene expression regulated by human alpha-fetoprotein enhancer directly linked to its promoter. Cancer Gene Ther 5, 301–306.PubMedGoogle Scholar
  21. 21.
    Caruso, M., Panis, Y., Gagandeep, S., 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.PubMedCrossRefGoogle Scholar
  22. 22.
    Kuriyama, S., Kikukawa, M., Masui, K., et al. (1999) Cancer gene therapy with HSV-TK/GCV system depends on T cell mediated immune responses and causes apoptotic death of tumour cells in vivo. Int. J. Cancer 83, 374–380.PubMedCrossRefGoogle Scholar
  23. 23.
    Van der Eb, M. M., Cramer, S. J., Vergouwe, Y., et al. (1998) Severe hepatic dysfunction after adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration. Gene Ther. 5, 4451–4458.Google Scholar
  24. 24.
    Kuriyama, S., Kikukawa, M., Masui, K., et al. (1998) Bystander effect caused by cytosine deaminase gene and 5-fluorocytosine in vitro is substantially mediated by generated 5-fluorouracil. Anticancer Res. 18, 3399–3409.PubMedGoogle Scholar
  25. 25.
    Block, A., Freund, C. T., Chen, S. H., et al. (2000) Gene therapy of metastatic comon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase. Cancer Gene Ther. 7, 438–445.PubMedCrossRefGoogle Scholar
  26. 26.
    Knowles, M. R., Hohneker, K. W., Zhou, Z., et al. (1995) A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N. Engl. J. Med. 333, 823–831.PubMedCrossRefGoogle Scholar
  27. 27.
    Tursz, T., Cesne, A. L., Baldeyrou, P., et al. (1996) Phase I study of a recombinant adenovirus-mediated gene transfer ilung cancer patients. J. Natl. Cancer Inst. 88, 1857–1863.PubMedCrossRefGoogle Scholar
  28. 28.
    Piccinino, F., Sagnelli, E., Pasquale, G., and Giusti, G. (1986) Complications following percutaneous liver biopsy. J. Hepatol. 2, 165–173.PubMedCrossRefGoogle Scholar
  29. 29.
    Perrault, J., McGill, D. B., Ott, B., and Taylor, W. F. (1978) Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 74, 103–106.PubMedGoogle Scholar
  30. 30.
    Barker D. D. and Berk A. J. (1987) Adenovirus proteins from both E1B reading frames are required for the transformation of rodent cells by viral infection and DNA transfection. Virology 156, 107–121.PubMedCrossRefGoogle Scholar
  31. 31.
    Lowe, S. W. (1997) Progress of the smart bomb cancer virus. Nature Med. 4, 1012–1013.Google Scholar
  32. 32.
    Rothmann, T., Hengstermann, A., Whitaker, N. J., et al. (1998) Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumour cells. J. Virol. 72, 9470–9478.PubMedGoogle Scholar
  33. 33.
    Goodrum, F. D. and Ornelles D. A. (1998) p53 Status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection. J. Virol. 72, 9479–9490.PubMedGoogle Scholar
  34. 34.
    Harada, J. N. and Berk, A. J. (1999) p53-Independent and-dependent requirments for E1B-55K in adenovirus type 5 replication. J. Virol. 72, 5333–5344.Google Scholar
  35. 35.
    Vollmer, C. M., Ribas, A., Butterfield, L. H., et al. (1999) p53 selective and nonselective replication of an E1B-deleted adenovirus in hepatocellular carcinoma. Cancer Res. 59, 4369–4374.PubMedGoogle Scholar
  36. 36.
    Heise, C., Sampson-Johannes, A., Williams, A., et al. (1997) ONYX-015, an E1B gene-attenuated adenovirus, causes tumour-specific cytolysis and antitumoural efficacy that can be augmented by standard chemotherapeutic agents. Nature Med. 3, 639–644.PubMedCrossRefGoogle Scholar
  37. 37.
    Ganly, I. (1999) Phase II trial of intratumoural infection with an E1B deleted adenovirus in patients with recurrent refractory head and neck cancer. Hum. Gene Ther. 10, 844.Google Scholar
  38. 38.
    Reid, T., Galanis, E., Abbruzzese, J., et al. (2001) Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial. Gene Ther. 8, 1618–1626.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Long R. Jiao
    • 1
  • Roman Havlik
    • 1
  • Joanna Nicholls
    • 1
  • Steen Lindkaer Jensen
    • 1
  • Nagy A. Habib
    • 1
  1. 1.Liver Surgery Section, Division of Surgery, Anaesthetics, and Intensive Care, Faculty of MedicineImperial College of Science, Technology, and MedicineLondonUK

Personalised recommendations