Skip to main content
SpringerLink
Log in

Experimental and Clinical Gene Therapies for Brain Tumors

  • Chapter
Gene Therapy for Neurological Disorders and Brain Tumors

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Experimental treatments employing viruses as antitumor agents were initially described in 1912, when vaccination with rabies virus was thought to have produced the disappearance of a large cervical carcinoma (1). A resurgence in the clinical use of viruses as a treatment for cancer occurred in the 1950s, subsequent to reports demonstrating the in vitro oncolytic capacity of viruses. These viruses included the Far East Russian encephalitis virus (2), Newcastle disease virus (3), polio virus (4), Egypt 101 virus (5), as well as herpesvirus (6). In one clinical study, an attenuated live rabies virus was used in 30 patients suffering from melanomatosis, with tumor regression seen in eight (7). One of the larger studies was performed at the National Institutes of Health and it involved the use of one of 10 human adenovirus serotypes (8). Thirty patients with epidermoid carcinoma of the cervix were enrolled and the adenovirus was injected by intratumoral, intra-arterial, or intravenous routes. An antitumor response, defined by the development of visible tumor necrosis at the site of injection, was observed in 26 of 30 patients. The most vigorous antitumor responses occurred in patients without pre-existing neutralizing antibodies to adenovirus. Unfortunately, antitumor responses were short-lived in the majority of treated cases. In 1974, wild-type live mumps virus was injected into the tumors of 90 terminally ill patients (9). Partial, but short-lived, regression was reported in 79 patients. In both of these large studies, no ill effects were observed in the normal tissues of treated patients. Despite these relatively interesting results, lack of enthusiasm for additional trials may have been produced by the uncertainty regarding mechanisms of action of virus-mediated oncolysis, lack of adequate manufacture of the viruses, and fear of virus-mediated oncogenicity. In 1970, Wright and Smith (10) postulated that witnessed antitumor effects were probably caused by a combination of viral lysis, local production of cytokines, and infiltration of immune effector cells. It is also possible that enhanced tumor antigen presentation might have contributed to this antitumor action, in a manner similar to the antiself (virus) immune response exhibited by mice transgenic for a viral antigen (11,12). Although our current state of knowledge permits us to better define the molecular events involved in virus-mediated antitumor effects, the prescient hypotheses of Wright and Smith regarding mechanisms of virus-mediated oncolysis remain current.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. De Pace, N. G. (1912) Sulla scomparsa di un enorme cancro vegetante del callo dell’ utero senza cura chirurgica. Ginecologia 9, 82–88.

    Google Scholar 

  2. Moore, A. E. (1949) The destructive effects of the virus of Russian Far East encephalitis on the transplantable mouse sarcoma 180. Cancer 2, 525–534.

    Article  PubMed  CAS  Google Scholar 

  3. Flanagan, A. D., Love, R., and Tesar, W. (1955) Propagation of Newscastle disease virus in Ehrlich ascites cells in vitro and in vivo. Proc. Soc. Exp. Bio. Med. 90, 82–86.

    CAS  Google Scholar 

  4. Scherer, W. F., Syverton, J. T. and Gey, G. O. (1953) Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J. Exp. Med. 97, 695–709.

    Article  PubMed  CAS  Google Scholar 

  5. Southam, C. M. and Moore, A. E. (1952) Clinical studies of viruses as antineoplastic agents, with particular reference to Egypt 101 virus. Cancer 5, 1025–1034.

    Article  PubMed  CAS  Google Scholar 

  6. Levaditi, C. and Nicolau, S. (1922) Affinite du virus herpetique pour les noeplasmes epitheliaux. Compt. rend. Soc. de bio. 87, 498–500.

    Google Scholar 

  7. Pack, G. T. (1950) Note on the experimental use of rabies vaccine for melanomatosis. Arch. Derm. Syph. 62, 694–695.

    Article  CAS  Google Scholar 

  8. Smith, R. R., Huebner, R. J., Rowe, W. P., Schatten, W. E., Thomas, L. B. (1956) Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 9, 1211–1218.

    Article  PubMed  Google Scholar 

  9. Asada, T. (1974) Treatment of human cancer with mumps virus. Cancer 34, 1907–1928.

    Article  PubMed  CAS  Google Scholar 

  10. Webb, H. E. and Smith, C. E. G. (1970) Viruses in the treatment of cancer. Lancet 1, 1206–1208.

    Article  PubMed  CAS  Google Scholar 

  11. Oldstone, M. B. A., Nerenberg, M., Southern, P., Price, J., Lewicki, H. (1991) Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65, 319–331.

    Article  PubMed  CAS  Google Scholar 

  12. Ohashi, P. S., Oehen, S., Buerki, K., Pircher, H., Ohashi, C. T., Odermatt, B., et al. (1991) Ablation of tolerance and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65, 305–317.

    Article  PubMed  CAS  Google Scholar 

  13. Moolten, F. L. (1986) Tumor chemosensitivity conferred by inserted thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res. 46, 5276–5281.

    PubMed  CAS  Google Scholar 

  14. Ezzeddine, Z. D., Martuza, R. L., Platika, D., et al. (1991) Selective killing of glioma cells in culture and in vivo by retrovirus transfer of the herpes simplex virus thymidine kinase gene. New Biol. 3, 608–614.

    PubMed  CAS  Google Scholar 

  15. Culver, K. W., Ram, Z., Wallbridge, S., et al. (1992) In vivo gene transfer with retroviral vector-produced cells for treatment of experimental brain tumors. Science 256, 1550–1552.

    Article  PubMed  CAS  Google Scholar 

  16. Takamiya, Y., Short, M. P., Moolten, F. L., Fleet, C., Mineta, R., Breakefield, X. O., and Martuza, R. L. (1993) An experimental model of retrovirus gene therapy for malignant brain tumors. J. Neurosurg. 79, 104–110.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Kim, K. J., Kim, S. H., Brown, S. L., and Freytag, S. O. (1994) Selective enhancement by an antiviral agent of the radiation-induced cell killing of human glioma cells transduced with HSV-tk gene. Cancer Res. 54, 6053–6056.

    PubMed  CAS  Google Scholar 

  21. Mroz, P. J. and Moolten, F. L. (1993) Retrovirally transduced Escherichia coli gpt genes combine selectability with chemosensitivity capable of mediating tumor eradication. Hum. Gene Ther. 4, 589–595.

    Article  PubMed  CAS  Google Scholar 

  22. Tamiya, T., Ono, Y., Wei, M. X., Mroz, P., Moolten, F. L., and Chiocca, E. A. (1996) The Escherichia Coli gpt gene sensitizes rat glioma cells to killing by 6-thioxanthine or 6-thioguanine. Cancer Gene Ther. 3,155–162.

    Google Scholar 

  23. Mullen, C. A., Kilstrup, M., and Blaese, R. M. (1992) Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc. Natl. Acad. Sci. USA 59, 33–37.

    Article  Google Scholar 

  24. Huber, B. E., Austin, E. A., Goode, S. S., Knick, V. C., Tibbels, S., and Richards, C. A. (1993) In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically modified to express cytosine deaminase. Cancer Res. 53, 4619–4626.

    PubMed  CAS  Google Scholar 

  25. Wei, M. X., Tamiya, T., Chase, M., Boviatsis, E. U., Chang, T. K. H., Hochberg, F. H., et al. (1994) Experimental tumor therapy in mice with the cyclophosphamide-activating cytochrome P450 2B 1 gene. Hum. Gene Ther. 5, 969–978.

    Article  PubMed  CAS  Google Scholar 

  26. Wei M. X., Tamiya, T., Rhee, R. J., Breakefield X. O., and Chiocca, E. A. (1995) Diffusible cytotoxic metabolites contribute to the in vitro bystander effect associated with cyclophosphamide/cytochrome P450 2B1 gene therapy. Clin. Cancer Res. 1, 1171–1177.

    PubMed  CAS  Google Scholar 

  27. Chen, L. and Waxman, D. J. (1995) Intratumoral activation and enhanced chemotherapeutic effect of oxazaphosphorines following cytochrome P450 gene transfer: development of a combined chemotherapy/cancer gene therapy strategy. Cancer Res. 55, 581–589.

    PubMed  CAS  Google Scholar 

  28. Chen, L., Waxman, D. J., Chen, D., and Kufe, D. W. (1996) Sensitization of human breast cancer cells to cyclophosphamide and ifosfamide by transfer of a liver cytochrome P450 gene. Cancer Res. 56, 1331–1340.

    PubMed  CAS  Google Scholar 

  29. Anlezark, G. M., Melton, R. G., Sherwood, R. F., Coles, B., Friedlos, F., and Knox, R. J. (1992) The bioactivation of 5-(aziridin-l-y1)-2,4-dinitrobenzamide (CB1954)-I: purification and properties of a nitroreducase enzyme from E. coli, a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT). Biochem. Pharmacol. 44, 2289–2295.

    Article  PubMed  CAS  Google Scholar 

  30. Manome, Y., Wen, P. Y., Dong, Y., Tanaka, T., Mitchell, B. S., Kufe, D. W., and Fine, H. A. (1996) Viral vector transduction of the human deoxycytidine kinase cDNA sensitizes glioma cells to the cytotoxic effects of cytosine arabinoside in vitro and in vivo. Nature Med. 2, 567–573.

    Article  PubMed  CAS  Google Scholar 

  31. Marais, R., Spooner, R. A., Light, Y., Martin, J., and Springer, C. J. (1996) Gene-directed enzyme prodrug therapy with a mustard prodrug/carboxypeptidase G2 combination. Cancer Res. 56, 4735–4742.

    PubMed  CAS  Google Scholar 

  32. Strand, S., Hofmann, W. J., Hug, H., Muller, M., Otto, G., Strand, D., et al. (1996) Lymphocyte apoptosis induced by CD95 (Apo-1/Fas) ligand-expressing tumor cells. A mechanism of immune evasion? Nature Med. 2, 1361–1366.

    Article  PubMed  CAS  Google Scholar 

  33. Hahne, M., Rimoldi, D., Schroter, M., Romereo, P., Schreier, M., French, L. E., et al. (1996) Melanoma cell expression of Fas (Apo-1/CD95) ligand: implications for tumor immune response. Science 274, 1363–1366.

    Article  PubMed  CAS  Google Scholar 

  34. Kuppner, M. C., Hamou, M. F., Sawamura, Y., Bodmer, S., and deTribolet, N. (1989) Inhibition of lymphocyte function byglioblastoma-derived transforming growth factor 132. J. Neurosurg. 71, 211–217.

    Article  PubMed  CAS  Google Scholar 

  35. Trojan, J., Johnson, T. R., Rudin, S. D., Ilan, J., Tykocinski, M. L., and Ilan, J. (1993) Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science 259, 94–97.

    Article  PubMed  CAS  Google Scholar 

  36. Beutler, A. S., Banck, M. S., Wedekind, D., Hedrich, H. J., and Aguzzi, A. (1997) Curing rat gliomas: immunotherapy or graft rejection? Science 276, 20, 21.

    Google Scholar 

  37. Wei, M. X., Tamiya, T., Hurford, R. K., Boviatsis, E. J., Tepper, R. I., and Chiocca, E. A. (1995) Enhancement of interleukin 4-mediated tumor regression in athymic mice by in situ retroviral gene transfer. Hum. Gene Ther. 6, 439–445.

    Article  Google Scholar 

  38. Yu, J., Wei, M. X., Chiocca, E. A., Martuza, R. L., and Tepper, R. L. (1993) Treatment of human glioma by engineered interleukin-4 secreting cells Cancer Res. 53, 3125–3128.

    PubMed  CAS  Google Scholar 

  39. Tjuvajev, J., Gansbacher B., Desai, R., Beattie B., Kaplitt, M. G., Matei, C., et al. (1995) RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. Cancer Res. 155, 1902–1910.

    Google Scholar 

  40. Pardoll, D. (1995) Paracrine cytokine adjuvants in cancer immunotherapy. Ann. Rev. Immunol. 13, 399–415.

    Article  CAS  Google Scholar 

  41. Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K., et al. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting antitumor immunity. Proc. Natl. Acad. Sci. USA 90, 3539–3543.

    Article  PubMed  CAS  Google Scholar 

  42. Fakhrai, H., Dorigo, O., Shawler, D. L., Lin, H., Mercola, D., Black, K. L., Royston, I., and Sobol, R. E. (1996) Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc. Natl. Acad. Sci. USA 93, 2909–2914.

    Article  PubMed  CAS  Google Scholar 

  43. Maione, T. E., Gray, G. S., Hunt, A. J., and Sharpe, R. J. (1991) Inhibition of tumor growth in mice by an analogue of platelet factor 4 that lacks affinity for heparin and retains potent angiostatic activity. Cancer Res. 51, 2077–2083.

    PubMed  CAS  Google Scholar 

  44. Milauer, B., Shawyer, L. K., Plate, K. H., Risau, W., and Ullrich, A. (1994) Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367, 576–578.

    Article  Google Scholar 

  45. Saleh, M., Stacker, S. A., and Wilks, A. F. (1996) Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res. 56, 393–401.

    PubMed  CAS  Google Scholar 

  46. Redekop, G. J. and Naus, C. C. G. (1995) Transfection with bFGF sense and antisense cDNA resulting in modification of malignant glioma growth. J. Neurosurg. 82, 83–90.

    Article  PubMed  CAS  Google Scholar 

  47. Samoto, K., Ikezaki, K., Ono, M., Shono, T., Kohno, K., Kuwano, M., and Fukui, M. (1995) Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res. 55, 1189–1193.

    PubMed  CAS  Google Scholar 

  48. Nabel, E. G., Yang, Z., Plautz, G., Forough, R., Zhan, Y., Haudenschild, C. C., Maciag, T., and Nabel G. J. (1993) Recombinant fibroblast growth factor-1 promotes intimai hyperplasia and angiogenesis in arteries in vivo. Nature 362, 844–846.

    Article  PubMed  CAS  Google Scholar 

  49. Hartwell, L. H. and Kastan, M. B. (1994) Cell cycle control and cancer. Science 266, 1821–1828.

    Article  PubMed  CAS  Google Scholar 

  50. Kastan, M. B., Onyekwere, O., Sidranski, D., Vogelstein, B., and Craig, R. W. (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51, 6304–6311.

    PubMed  CAS  Google Scholar 

  51. Dulic, V., Kaufmann, W. K., Wilson, S. J., Tisty, T. D., Lees, E., Harper, J. W., Elledge, S. J., and Reed, S. I. (1994) p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76, 1013–1023.

    Google Scholar 

  52. el-Deity, W. S., Harper, J. W., O’Connor, P. M., Velculescu, V. E., Canman, C. E., Jackman, J., et al. (1994) WAF1/CIP1 is induced in p53-mediated 01 arrest and apoptosis. Cancer Res. 54, 1169–1174.

    Google Scholar 

  53. Kastan, M. B., Zhan, Q., el-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., et al. (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71, 587–597.

    Article  PubMed  CAS  Google Scholar 

  54. Smith, M. L., Chen, I. T., Zhan, Q., Bae, I., Chen, C. Y., Gilmer, T. M., et al. (1994) Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science 266, 1376–1380.

    Article  PubMed  CAS  Google Scholar 

  55. Wang, X. W., Forrester, K., Yeh, H., Feitelson, M. A., Gu, J., and Harris, C. C. (1994) Hepatitis B virus protein X inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc. Natl. Acad. Sci. USA 91, 2230–2234.

    Article  PubMed  CAS  Google Scholar 

  56. Wang, X. W., Yeh, H., Schaeffer, L., Roy, R., Moncollin, V., Egly, J., et al. (1995) p53 modulation of TFIIH-associated nucleotide excision repair activity. Nature Genet. 10, 188–195.

    Google Scholar 

  57. Rosenfeld, M. R., Meneses, P., Dalmau, J., Drobjnak, M., Cordon-Cardo, C., and Kaputt, M. G. (1995) Gene transfer of wild-type p53 results in restoration of tumor suppressor function in a medulloblastoma cell line. Neurology 45, 1533–1539.

    Article  PubMed  CAS  Google Scholar 

  58. Gomez-Manzano, C., Fueyo, J., Kyritsis, A. P., Steck, P. A., Roth, J. A., McDonnell, T. J., et al. (1996) Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res. 56, 694–699.

    PubMed  CAS  Google Scholar 

  59. Moore, A. E. (1949) Effect of inoculation of the viruses of influenza A and herpes simplex on the growth of transplantable tumors in mice. Cancer 1, 516–524.

    Article  Google Scholar 

  60. Martuza, R. L., Malick, A., Markert, J. M., Ruffner, K. L., and Coen, D. M. (1991) Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252, 854–856.

    Article  PubMed  CAS  Google Scholar 

  61. Dou, 0.-P., Markell, P. J., and Pardee, A. B. (1992) Thymidine kinase transcription is regulated at Gl/S phase by a complex that contains retinoblastoma-like protein and a cdc2 kinase. Proc. Natl. Acad. Sci. USA 89, 3256–3260.

    Article  Google Scholar 

  62. Coen, D. M., Kosz-Vnenchak, M., Jacobson, J. G., Leib, D. A., Bograd, C. L., Schaffer, P. A., Tyler, K. L., and Knipe, D. M. (1989) Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc. Natl. Acad. Sci. USA 86, 4736–4740.

    Article  PubMed  CAS  Google Scholar 

  63. Bjorklund, S., Skog, S., Tribukait, B., and Thelander, L. (1990) S-phase-specific expression of mammalian ribonucleotide reductase R1 and R2 subunit mRNAs. Biochemistry 29, 5452–5458.

    Article  PubMed  CAS  Google Scholar 

  64. Elledge, S. J., Zhou, Z., and Allen, J. B. (1992) Ribonucleotide reductase: regulation, regulation, regulation. TIBS 17, 119–123.

    PubMed  CAS  Google Scholar 

  65. Boviatsis, E. J., Scharf, J. M., Chase, M., Harrington, K., Breakefield X. O., and Chiocca, E. A. (1994) Antitumor activity and reporter gene transfer into rat brain neoplasms inoculated with herpes simplex virus vectors defective in thymidine kinase or ribonucleotide reductase. Gene Ther. 1, 323–331.

    PubMed  CAS  Google Scholar 

  66. Boviatsis, E. J., Park, J. S., Sena-Esteves, M., Kramm, C., Chase, M., Efird, J., et al. (1994) Long-term survival of rats harboring brain tumors treated with ganciclovir and a herpes simplex virus vector that maintains an intact thymidine kinase gene. Cancer Res. 54, 5745–5751.

    PubMed  CAS  Google Scholar 

  67. Kaplitt, M. G., Tjuvajev, J. G., Leib, D. A., Berk, D. A., Berk, J., Pettigrew, K. D., et al. (1994) Mutant herpes simplex virus induced regression of tumors growing in immunocompetent rats. J. Neurooncol. 19, 137–147.

    Article  PubMed  CAS  Google Scholar 

  68. Mineta, T., Rabkin, S. D., and Martuza, R. L. (1994) Treatment of malignant glioma using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex virus mutant. Cancer Res. 54, 3936–3966.

    Google Scholar 

  69. Chou, J. and Roizman, B. (1992) The gammal 34.5 gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programmed cell death in neuronal cells. Proc. Natl. Acad. Sci. USA 89, 3266–3270.

    Article  PubMed  CAS  Google Scholar 

  70. Chou, J. and Roizman, B. (1994) Herpes simplex virus 1 gammal 34.5 gene function, which blocks the host response to infection, maps in the homologous domain of the genes expressed during growth arrest and DNA damage. Proc. Natl. Acad. Sci. USA 91, 5247–5251.

    Article  PubMed  CAS  Google Scholar 

  71. Markert, J. M., Malick, A., Coen, D. M., and Martuza, R. L. (1993) Reduction and elimination of encephalitis in an experimental glioma therapy model with attenuated herpes simplex mutants that retain susceptibility to acyclovir. Neurosurgery 32, 597–602.

    Article  PubMed  CAS  Google Scholar 

  72. Kesari, S., Randazzo, B. P., Valyi-Nagy, T., Huang, Q. S., Brown, S. M., MacLean, A. R., et al. (1995) Therapy of experimental brain tumors using a neuroattenuated herpes simplex virus mutant. Lab. Invest. 73, 636–648.

    PubMed  CAS  Google Scholar 

  73. Mineta, T., Rabkin, S. D., Yazaki, T., Hunter, W. D., and Martuza, R. L. (1995) Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nature Med. 1, 938–943.

    Article  PubMed  CAS  Google Scholar 

  74. Rabkin, S. D., Hunter, W. D., New, K. C., Toda, M., and Martuza, R. L. (1996) A “safe” herpes simplex virus (HSV) vector for tumor therapy or gene delivery in the brain. Soc. Neurosci. Abstracts 22, 370. 9.

    Google Scholar 

  75. Lorence, R. M., Katubig, B. B., Reichard, K. W., Reyes, H. M., Puangshab, A., Sassetti, M. D., Walter, R. J., and Peeples, M. E. (1994) Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy. Cancer Res. 54, 6017–6021.

    PubMed  CAS  Google Scholar 

  76. Lorence, R. M., Reichard, K. W., Katubig, B. B., Reyes, H. M., Puangshab, A., Mitchell, B. R., et al. (1994) Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J. Natl. Cancer Inst. 86, 1228–1233.

    Article  PubMed  CAS  Google Scholar 

  77. Kao, C. C., Yew, P. R., and Berk, A. J. (1990) Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology 179, 806–814.

    Google Scholar 

  78. Yew, P. R., Kao, C. C., and Berk, A. J. (1990) Dissection of functional domains in the adenovirus 2 early 1B 55K polypeptide by suppressor-linked insertional mutagenesis. Virology 179, 795–805.

    Article  PubMed  CAS  Google Scholar 

  79. Bischoff, J. R., Kirn, D. H., Kim, D. H., Williams, A., Heise, C., Horn, S., et al. (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274, 373–376.

    Article  PubMed  CAS  Google Scholar 

  80. Oldfield, E. H., Ram, Z., Culver, K. W., Blaese, R. M., DeVroom, H. L., and Anderson, W. F. (1993) 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 

  81. Ram, Z., Culver, K., Oshiro, E., Viola, J., DeVroom, H., Otto, E., et al. (1995) Summary of results and conclusions of the gene therapy of malignant brain tumors: a clinical study. J. Neurosurg. 82, 343A (Abstract).

    Google Scholar 

  82. Berger, M. S., Prados, M., Van Gilder, J. C., Warnick, R. E., Link, C. J., and Marcus, S. G. (1997) Gene therapy for the treatment of recurrent glioblastoma multiforme with in vivo transduction using the herpes simplex-thymidine kinase gene/ganciclovir system. J. Neurosurg. 86, 378A (Abstract).

    Google Scholar 

  83. Eck, S. L., Alavi, J. B., Alavi, A., Davis, A., Hackney, D., and Judy, K. (1996) Treatment of advanced human CNS malignancies with the recombinant adenovirus H5.010RSVTK: a phase I trial. Hum. Gene Ther. 7, 1465–1482.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. E. Antonio Chiocca
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Molecular Neuro-Oncology, Neurosurgical Service, Massachussetts General Hospital, Harvard Medical School, Boston, MA, USA

    E. Antonio Chiocca MD, PhD

  2. Neurogenetics Unit, Massachussetts General Hospital, Harvard Medical Center, Boston, MA, USA

    Xandra O. Breakefield PhD

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chiocca, E.A. (1998). Experimental and Clinical Gene Therapies for Brain Tumors. In: Chiocca, E.A., Breakefield, X.O. (eds) Gene Therapy for Neurological Disorders and Brain Tumors. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-478-8_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-478-8_11

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5314-1

  • Online ISBN: 978-1-59259-478-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation