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:

Clinical trials of gene therapy, virotherapy, and immunotherapy for malignant gliomas

Cancer Gene Therapy volume 13, pages 539–554 (2006)Cite this article

Abstract

Despite advances in surgical and adjuvant therapy, the prognosis for malignant gliomas remains dismal. This gloomy scenario has been recently brightened by the increasing understanding of the genetic and biological mechanisms at the basis of brain tumor development. These findings are being translated into innovative therapeutic approaches, including gene therapy, virotherapy, and vaccination, some of which have already been experimented in clinical trials. The advantages and disadvantages of all these different therapeutic modalities for malignant gliomas will be critically discussed, providing perspective for future investigations.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. De Angelis LM . Brain tumors. N Engl J Med 2001; 344: 114–123.

    CAS  Google Scholar 

  2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987–996.

    CAS  PubMed  Google Scholar 

  3. Oldfield EH, Ram Z, Culver KW, Blaese RM, DeVroom HL, Anderson WF . Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther 1993; 4: 39–69.

    CAS  PubMed  Google Scholar 

  4. Barzon L, Boscaro M, Palù G . Endocrine aspects of cancer gene therapy. Endocr Rev 2004; 25: 1–44.

    CAS  PubMed  Google Scholar 

  5. Pulkkanen KJ, Yla-Herttuala S . Gene therapy for malignant glioma: current clinical status. Mol Ther 2005; 12: 585–598.

    CAS  PubMed  Google Scholar 

  6. Izquierdo M, Martin V, de Felipe P, Izquierdo JM, Perez-Higueras A, Cortes ML et al. Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/ganciclovir gene therapy. Gene Therapy 1996; 3: 491–495.

    CAS  PubMed  Google Scholar 

  7. Ram Z, Culver KW, Oshiro EM, Viola JJ, DeVroom HL, Otto E et al. Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat Med 1997; 3: 1354–1361.

    CAS  PubMed  Google Scholar 

  8. Klatzmann D, Valery CA, Bensimon G, Marro B, Boyer O, Mokhtari K et al. A phase I/II study of herpes simplex virus type 1 thymidine kinase ‘suicide’ gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma. Hum Gene Ther 1998; 9: 2595–2604.

    CAS  PubMed  Google Scholar 

  9. Shand N, Weber F, Mariani L, Bernstein M, Gianella-Borradori A, Long Z et al. A phase 1–2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European–Canadian Study Group. Hum Gene Ther 1999; 10: 2325–2335.

    Article  CAS  PubMed  Google Scholar 

  10. Trask TW, Trask RP, Aguilar-Cordova E, Shine HD, Wyde PR, Goodman JC et al. Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther 2000; 1: 195–203.

    CAS  PubMed  Google Scholar 

  11. Harsh GR, Deisboeck TS, Louis DN, Hilton J, Colvin M, Silver JS et al. Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study. J Neurosurg 2000; 92: 804–811.

    CAS  PubMed  Google Scholar 

  12. Packer RJ, Raffel C, Villablanca JG, Tonn JC, Burdach SE, Burger K et al. Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration. J Neurosurg 2000; 92: 249–254.

    CAS  PubMed  Google Scholar 

  13. Sandmair AM, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M et al. Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Hum Gene Ther 2000; 11: 2197–2205.

    CAS  PubMed  Google Scholar 

  14. Rainov NG . A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 2000; 11: 2389–2401.

    CAS  PubMed  Google Scholar 

  15. Floeth FW, Shand N, Bojar H, Prisack HB, Felsberg J, Neuen-Jacob E et al. Local inflammation and devascularization – in vivo mechanisms of the ‘bystander effect’ in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma. Cancer Gene Ther 2001; 8: 843–851.

    CAS  PubMed  Google Scholar 

  16. Smitt PS, Driesse M, Wolbers J, Kros M, Avezaat C . Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir. Mol Ther 2003; 7: 851–858.

    CAS  PubMed  Google Scholar 

  17. Prados MD, McDermott M, Chang SM, Wilson CB, Fick J, Culver KW et al. Treatment of progressive or recurrent glioblastoma multiforme in adults with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration: a phase I/II multi-institutional trial. J Neurooncol 2003; 65: 269–278.

    PubMed  Google Scholar 

  18. Germano IM, Fable J, Gultekin SH, Silvers A . Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. J Neurooncol 2003; 65: 279–289.

    PubMed  Google Scholar 

  19. Lang FF, Bruner JM, Fuller GN, Aldape K, Prados MD, Chang S et al. Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol 2003; 21: 2508–2518.

    CAS  PubMed  Google Scholar 

  20. Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 2001; 358: 727–729.

    CAS  PubMed  Google Scholar 

  21. Voges J, Reszka R, Gossmann A, Dittmar C, Richter R, Garlip G et al. Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma. Ann Neurol 2003; 54: 479–487.

    CAS  PubMed  Google Scholar 

  22. Immonen A, Vapalahti M, Tyynela K, Hurskainen H, Sandmair A, Vanninen R et al. AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study. Mol Ther 2004; 10: 967–972.

    CAS  PubMed  Google Scholar 

  23. Palu G, Cavaggioni A, Calvi P, Franchin E, Pizzato M, Boschetto R et al. Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans. Gene Therapy 1999; 6: 330–337.

    CAS  PubMed  Google Scholar 

  24. Colombo F, Barzon L, Franchin E, Pacenti M, Pinna V, Danieli D et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results. Cancer Gene Ther 2005; 12: 835–848.

    CAS  PubMed  Google Scholar 

  25. Long Z, Lu P, Grooms T, Mychkovsky I, Westley T, Fitzgerald T et al. Molecular evaluation of biopsy and autopsy specimens from patients receiving in vivo retroviral gene therapy. Hum Gene Ther 1999; 10: 733–740.

    CAS  PubMed  Google Scholar 

  26. Tamura M, Ikenaka K, Tamura K, Yoshimatsu T, Miyao Y, Kishima H et al. Transduction of glioma cells using a high-titer retroviral vector system and their subsequent migration in brain tumors. Gene Therapy 1998; 5: 1698–1704.

    CAS  PubMed  Google Scholar 

  27. Stefani A-L, Barzon L, Castagliuolo I, Guido M, Pacenti M, Parolin C et al. Systemic efficacy of combined suicide/cytokine gene therapy in a murine model of hepatocellular carcinoma. J Hepatol 2005; 42: 728–735.

    CAS  PubMed  Google Scholar 

  28. Long Z, Li LP, Grooms T, Lockey C, Nader K, Mychkovsky I et al. Biosafety monitoring of patients receiving intracerebral injections of murine retroviral vector producer cells. Hum Gene Ther 1998; 9: 1165–1172.

    CAS  PubMed  Google Scholar 

  29. Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH . Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 1994; 91: 2076–2080.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Colombo F, Zanusso M, Casentini L, Cavaggioni A, Franchin E, Calvi P et al. Gene stereotactic neurosurgery for recurrent malignant gliomas. Stereotact Funct Neurosurg 1997; 68: 245–251.

    CAS  PubMed  Google Scholar 

  31. Barba D, Hardin J, Sadelain M, Gage FH . Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci USA 1994; 91: 4348–4352.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Rainov NG, Kramm CM, Banning U, Riemann D, Holzhausen HJ, Heidecke V et al. Immune response induced by retrovirus-mediated HSV-tk/GCV pharmacogene therapy in patients with glioblastoma multiforme. Gene Therapy 2000; 7: 1853–1858.

    CAS  PubMed  Google Scholar 

  33. Kramm CM, Korholz D, Rainov NG, Niehues T, Fischer U, Steffens S et al. Systemic activation of the immune system during ganciclovir treatment following intratumoral herpes simplex virus type 1 thymidine kinase gene transfer in an adolescent ependymoma patient. Neuropediatrics 2002; 33: 6–9.

    CAS  PubMed  Google Scholar 

  34. Chiocca EA . Oncolytic viruses. Nat Rev Cancer 2002; 2: 938–950.

    PubMed  Google Scholar 

  35. Markert JM, Medlock MD, Rabkin SD, Gillespie GY, Todo T, Hunter WD et al. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Therapy 2000; 7: 867–874.

    CAS  PubMed  Google Scholar 

  36. Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D et al. Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Therapy 2000; 7: 859–866.

    CAS  PubMed  Google Scholar 

  37. Papanastassiou V, Rampling R, Fraser M, Petty R, Hadley D, Nicoll J et al. The potential for efficacy of the modified (ICP 34.5(−)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study. Gene Therapy 2002; 9: 398–406.

    CAS  PubMed  Google Scholar 

  38. Harrow S, Papanastassiou V, Harland J, Mabbs R, Petty R, Fraser M et al. HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival. Gene Therapy 2004; 11: 1648–1658.

    CAS  PubMed  Google Scholar 

  39. Chiocca EA, Abbed KM, Tatter S, Louis DN, Hochberg FH, Barker F et al. A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther 2004; 10: 958–966.

    CAS  PubMed  Google Scholar 

  40. Csatary LK, Bakacs T . Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma. JAMA 1999; 281: 1588–1589.

    CAS  PubMed  Google Scholar 

  41. Csatary LK, Gosztonyi G, Szeberenyi J, Louis DN, Hochberg FH, Barker F et al. MTH-68/H oncolytic viral treatment in human high-grade gliomas. J Neurooncol 2004; 67: 83–93.

    CAS  PubMed  Google Scholar 

  42. Farassati F, Yang A, Lee PWK . Oncogenes in Ras signaling pathway dictate host-cell permissiveness to herpes simplex type 1. Nat Cell Biol 2001; 3: 745–750.

    CAS  PubMed  Google Scholar 

  43. Whitley RJ, Kern ER, Chatterjee S, Chou J, Roizman B . Replication, establishment of latency, and induced reactivation of herpes simplex virus gamma 1 34.5 deletion mutants in rodent models. J Clin Invest 1993; 91: 2837–2843.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Goldstein DJ, Weller SK . Factors present in herpes simplex virus type 1-infected cells can compensate for the loss of the large subunit of the viral ribonucleotide reductase: characterization of an ICP6 deletion mutant. Virology 1988; 166: 41–51.

    CAS  PubMed  Google Scholar 

  45. Mineta T, Rabkin SD, Martuza RL . Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant. Cancer Res 1991; 54: 3963–3966.

    Google Scholar 

  46. Harland J, Papanastassiou V, Brown SM . HSV1716 persistence in primary human glioma cells in vitro. Gene Therapy 2002; 9: 1194–1198.

    CAS  PubMed  Google Scholar 

  47. McKie EA, MacLean AR, Lewis AD, Cruickshank G, Rampling R, Barnett SC et al. Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours – evaluation of a potentially effective clinical therapy. Br J Cancer 1996; 74: 745–752.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Detta A, Harland J, Hanif I, Brown SM, Cruickshank G . Proliferative activity and in vitro replication of HSV1716 in human metastatic brain tumours. J Gene Med 2003; 5: 681–689.

    PubMed  Google Scholar 

  49. Reichard KW, Lorence RM, Cascino CJ, Peeples ME, Walter RJ, Fernando MB et al. Newcastle disease virus selectively kills human tumor cells. J Surg Res 1992; 52: 448–453.

    CAS  PubMed  Google Scholar 

  50. Schirrmacher V, Haas C, Bonifer R, Ahlert T, Gerhards R, Ertel C . Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus. Gene Therapy 1999; 6: 63–73.

    CAS  PubMed  Google Scholar 

  51. Washburn B, Schirrmacher V . Human tumor cell infection by Newcastle Disease Virus leads to upregulation of HLA and cell adhesion molecules and to induction of interferons, chemokines and finally apoptosis. Int J Oncol 2002; 21: 85–93.

    CAS  PubMed  Google Scholar 

  52. Cassell WA, Garrett RE . Newcastle disease virus as an antineoplastic agent. Cancer 1965; 18: 863–868.

    Google Scholar 

  53. Csatary LK . Viruses in the treatment of cancer. Lancet 1971; 2: 825.

    CAS  PubMed  Google Scholar 

  54. Pecora AL, Rizvi N, Cohen GI, Meropol NJ, Sterman D, Marshall JL et al. Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol 2002; 20: 2251–2266.

    CAS  PubMed  Google Scholar 

  55. Csatary LK, Eckhardt S, Bukosza I, Czegledi F, Fenyvesi C, Gergely P et al. Attenuated veterinary virus vaccine for the treatment of cancer. Cancer Detect Prev 1993; 17: 619–627.

    CAS  PubMed  Google Scholar 

  56. Csatary LK, Moss RW, Beuth J, Torocsik B, Szeberenyi J, Bakacs T . Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Res 1999; 19: 635–638.

    CAS  PubMed  Google Scholar 

  57. Ehtesham M, Black KL, Yu JS . Recent progress in immunotherapy for malignant glioma: treatment strategies and results from clinical trials. Cancer Control 2004; 11: 192–207.

    PubMed  Google Scholar 

  58. Holladay FP, Heitz-Turner T, Bayer WL, Wood GW . Autologous tumor cell vaccination combined with adoptive cellular immunotherapy in patients with grade III/IV astrocytoma. J Neurooncol 1996; 27: 179–189.

    CAS  PubMed  Google Scholar 

  59. Plautz GE, Barnett GH, Miller DW, Cohen BH, Prayson RA, Krauss JC et al. Systemic T cell adoptive immunotherapy of malignant gliomas. J Neurosurg 1998; 89: 42–51.

    CAS  PubMed  Google Scholar 

  60. Plautz GE, Miller DW, Barnett GH, Stevens GH, Maffett S, Kim J et al. T cell adoptive immunotherapy of newly diagnosed gliomas. Clin Cancer Res 2000; 6: 2209–2218.

    CAS  PubMed  Google Scholar 

  61. Wood GW, Holladay FP, Turner T, Wang YY, Chiga M . A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent grade III/IV astrocytoma. J Neurooncol 2000; 48: 113–120.

    CAS  PubMed  Google Scholar 

  62. Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol 2001; 19: 2189–2200.

    CAS  PubMed  Google Scholar 

  63. Schneider T, Gerhards R, Kirches E, Raimund Firsching R . Preliminary results of active specific immunization with modified tumor cell vaccine in glioblastoma multiforme. J Neurooncol 2001; 53: 39–46.

    CAS  PubMed  Google Scholar 

  64. Steiner HH, Bonsanto MM, Beckhove P, Brysch M, Geletneky K, Ahmadi R et al. Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit. J Clin Oncol 2004; 22: 4272–4281.

    PubMed  Google Scholar 

  65. Yu JS, Wheeler CJ, Zeltzer PM, Ying H, Finger DN, Lee PK et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res 2001; 61: 842–847.

    CAS  PubMed  Google Scholar 

  66. Wheeler CJ, Das A, Liu G, Yu JS, Black KL . Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res 2004; 10: 5316–5326.

    CAS  PubMed  Google Scholar 

  67. Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T et al. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial. Br J Cancer 2003; 89: 1172–1179.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Yu JS, Liu G, Ying H, Yong WH, Black KL, Wheeler CJ . Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res 2004; 64: 4973–4979.

    CAS  PubMed  Google Scholar 

  69. Rutkowski S, De Vleeschouwer S, Kaempgen E, Wolff JE, Kuhl J, Demaerel P et al. Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study. Br J Cancer 2004; 91: 1656–1662.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M, Kobayashi T et al. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin Cancer Res 2005; 11: 4160–4167.

    CAS  PubMed  Google Scholar 

  71. Kikuchi T, Akasaki Y, Irie M, Homma S, Abe T, Ohno T . Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother 2001; 50: 337–344.

    CAS  PubMed  Google Scholar 

  72. Kikuchi T, Akasaki Y, Abe T, Fukuda T, Saotome H, Ryan JL et al. Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12. J Immunother 2004; 27: 452–459.

    CAS  PubMed  Google Scholar 

  73. Ehtesham M, Kabos P, Gutierrez MA, Samoto K, Black KL, Yu JS . Intratumoral dendritic cell vaccination elicits potent tumoricidal immunity against malignant glioma in rats. J Immunother 2003; 26: 107–116.

    PubMed  Google Scholar 

  74. Young H, Kaplan A, Regelson W . Immunotherapy with autologous white cell infusion (‘lymphocytes’) in the treatment of recurrent glioblastoma multiforme: a preliminary report. Cancer 1977; 40: 1037–1044.

    CAS  PubMed  Google Scholar 

  75. Neuwelt EA, Clark K, Kirkpatrick JB, Toben H . Clinical studies of intratechal autologous lymphocyte infusions in patients with malignant glioma: a toxicity study. Ann Neurol 1978; 4: 307–312.

    CAS  PubMed  Google Scholar 

  76. Vaquero J, Martinez R, Ramiro J, Salazar FG, Barbolla L, Regidor C . Immunotherapy of glioblastoma with intratumoural administration of autologous lymphocytes and human lymphoblastoid interferon. A further clinical study. Acta Neurochir (Wien) 1991; 109: 42–45.

    CAS  Google Scholar 

  77. Hayes RL, Koslow M, Hiesiger EM, Hymes KB, Hochster HS, Moore EJ et al. Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer 1995; 76: 840–852.

    CAS  PubMed  Google Scholar 

  78. Merchant RE, Grant AJ, Merchant LH, Young HF . Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2. Cancer 1988; 62: 665–671.

    CAS  PubMed  Google Scholar 

  79. Barba D, Saris SC, Holder C, Rosenberg SA, Oldfield EH . Intratumoral LAK cell and interleukin-2 therapy of human gliomas. J Neurosurg 1989; 70: 175–182.

    CAS  PubMed  Google Scholar 

  80. Quattrocchi KB, Miller CH, Cush S, Bernard SA, Dull ST, Smith M et al. Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neurooncol 1999; 45: 141–157.

    CAS  PubMed  Google Scholar 

  81. Kruse CA, Schiltz PM, Bellgrau D, Kong Q, Kleinschmidt-DeMasters BK . Intracranial administrations of single or multiple source allogeneic cytotoxic T lymphocytes: chronic therapy for primary brain tumors. J Neurooncol 1994; 19: 161–168.

    CAS  PubMed  Google Scholar 

  82. Kruse CA, Cepeda L, Owens B, Johnson SD, Stears J, Lillehei KO . Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2. Cancer Immunol Immunother 1997; 45: 77–87.

    CAS  PubMed  Google Scholar 

  83. Sobol RE, Fakhrai H, Shawler D, Gjerset R, Dorigo O, Carson C et al. Interleukin-2 gene therapy in a patient with glioblastoma. Gene Therapy 1995; 2: 164–167.

    CAS  PubMed  Google Scholar 

  84. Okada H, Lieberman FS, Edington HD, Witham TF, Wargo MJ, Cai Q et al. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy. J Neurooncol 2003; 64: 13–20.

    PubMed  Google Scholar 

  85. Resnicoff M, Sell C, Rubini M, Coppola D, Ambrose D, Baserga R et al. Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res 1994; 54: 1235–1242.

    Google Scholar 

  86. Resnicoff M, Tjuvajev J, Rotman HL, Abraham D, Curtis M, Aiken R et al. Regression of C6 rat brain tumors by cells expressing an antisense insulin-like growth factor I receptor RNA. J Exp Ther Oncol 1996; 1: 385–389.

    CAS  PubMed  Google Scholar 

  87. Akasaki Y, Black KL, Yu JS . Dendritic cell-based immunotherapy for malignant gliomas. Expert Rev Neurother 2005; 5: 497–508.

    CAS  PubMed  Google Scholar 

  88. Banchereau J, Palucka K . Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 2005; 5: 296–306.

    CAS  PubMed  Google Scholar 

  89. De Vleeschouwer S, Van Calenbergh F, Demaerel P, Flamen P, Rutkowski S, Kaempgen E et al. Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy. Case report. J Neurosurg 2004; 100 (Suppl Pediatrics): 492–497.

    PubMed  Google Scholar 

  90. Tsugawa T, Kuwashima N, Sato H, Fellows-Mayle WK, Dusak JE, Okada K et al. Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response. Gene Therapy 2004; 11: 1551–1558.

    CAS  PubMed  Google Scholar 

  91. Hesdorffer C, Ayello J, Ward M, Kaubisch A, Vahdat L, Balmaceda C et al. Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation. J Clin Oncol 1998; 16: 165–172.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from FIRB no. RBNE0127YS-006 and from IOV (Istituto Oncologico Veneto) to G Palù.

Author information

Authors and Affiliations

  1. Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy

    L Barzon & G Palù

  2. Division of Neurosurgery, San Bortolo Hospital, Vicenza, Italy

    M Zanusso & F Colombo

Authors
  1. L Barzon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Zanusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Colombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Palù
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L Barzon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barzon, L., Zanusso, M., Colombo, F. et al. Clinical trials of gene therapy, virotherapy, and immunotherapy for malignant gliomas. Cancer Gene Ther 13, 539–554 (2006). https://doi.org/10.1038/sj.cgt.7700930

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700930

Keywords

This article is cited by

Search

Advanced search

Quick links