Skip to main content
SpringerLink
Log in

Clinical Trials of Adenoviruses in Brain Tumors: A Review of Ad-p53 and Oncolytic Adenoviruses

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Adenoviruses have been critical in the development of the molecular approaches to brain tumors. They have been engineered to function as vectors for delivering therapeutic genes in gene therapy strategies, and as direct cytotoxic agents in oncolytic viral therapies. This review outlines the uses of adenoviruses in brain tumor therapy by examining clinical trials of adenovirus-mediated p53 gene therapy and by reviewing the application of two conditionally replicative adenoviruses (CRAds) ONYX-015 and Delta 24 in brain tumors. The potential clinical use of CRAds that deliver trangenes, particularly p53, is also discussed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Walker AE, Robins M, Weinfeld FD: Epidemiology of brain tumors: the national survey of intracranial neoplasms. Neurology 35: 219-226, 1985

    Google Scholar 

  2. Russell WC: Update on adenovirus and its vectors. J Gen Virol 81: 2573-2604, 2000

    Google Scholar 

  3. Wu Q, Moyana T, Xiang J: Cancer gene therapy by adenovirus-mediated gene transfer. Curr Gene Ther 1: 101-122, 2001

    Google Scholar 

  4. Suzuki K, Alemany R, Yamamoto M, Curiel DT: The presence of the adenovirus E3 region improves the oncolytic potency of conditionally replicative adenoviruses. Clin Cancer Res 8: 3348-3359, 2002

    Google Scholar 

  5. Bonetta L: Leukemia case triggers tighter gene-therapy controls. Natl Med 8: 1189, 2002

    Google Scholar 

  6. Farzaneh F, Trefzer U, Sterry W, Walden P: Gene therapy of cancer. Immunol Today 19: 294-296, 1998

    Google Scholar 

  7. Fueyo J, Gomez-Manzano C, Liu TJ, Yung WK: Delivery of cell cycle genes to block astrocytoma growth.J Neuro-Oncol 51: 277-287, 2001

    Google Scholar 

  8. McCormick F: Cancer gene therapy: fringe or cutting edge? Natl Rev Cancer 1: 130-141, 2001

    Google Scholar 

  9. Vorburger SA, Hunt KK: Adenoviral gene therapy. Oncologis 7: 46-59, 2002

    Google Scholar 

  10. Trask TW, Trask RP, Aguilar-Cordova E, Shine HD, Wyde PR, Goodman JC, Hamilton WJ, Rojas-Martinez A, Chen SH, Woo SL, Grossman RG: Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther 1: 195-203, 2000

    Google Scholar 

  11. Sandmair AM, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M, Hurskainen H, Tyynela K, Turunen M, Vanninen R, Lehtolainen P, Paljarvi L, Johansson R, Vapalahti M, Yla-Herttuala S: Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Hum Gene Ther 11: 2197-2205, 2000

    Google Scholar 

  12. Prives C, Hall PA: The p53 pathway. J. Pathol 187: 112-126, 1999

    Google Scholar 

  13. Stewart ZA, Pietenpol JA: p53 Signaling and cell cycle checkpoints. Chem Res Toxicol 14: 243-263, 2001

    Google Scholar 

  14. Vogelstein B, Lane D, Levine AJ:Surfing the p53 network. Nature 408: 307-310, 2000

    Google Scholar 

  15. Zhang WW, Alemany R, Wang J, Koch PE, Ordonez NG, Roth JA: Safety evaluation of Ad5CMV-p53 in vitro and in vivo. Hum Gene Ther 6: 155-164, 1995

    Google Scholar 

  16. Merritt JA, Roth JA, Logothetis CJ: Clinical evaluation of adenoviral-mediated p53 gene transfer: reviewof INGN 201 studies. Semin Oncol 28: 105-114, 2001

    Google Scholar 

  17. Blagosklonny MV, el-Deiry WS: In vitro evaluation of a p53-expressing adenovirus as an anti-cancer drug. Int J Cancer 67: 386-392, 1996

    Google Scholar 

  18. Parker LP, Wolf JK, Price JE: Adenoviral-mediated gene therapy with Ad5CMVp53 and Ad5CMVp21 in combination with standard therapies in human breast cancer cell lines. Ann Clin Lab Sci 30: 395-405, 2000

    Google Scholar 

  19. Fujiwara T, Grimm EA, Mukhopadhyay T, Zhang WW, Owen-Schaub LB, Roth JA: Induction of chemosensitivity in human lung cancer cells in vivo by adenovirusmediated transfer of the wild-type p53 gene. Cancer Res 54: 2287-2291, 1994

    Google Scholar 

  20. Clayman GL, Liu TJ, Overholt SM, Mobley SR, Wang M, Janot F, Goepfert H: Gene therapy for head and neck cancer. Comparing the tumor suppressor gene p53 and a cell cycle regulator WAF1/CIP1 (p21). Arch Otolaryngol Head Neck Surg 122: 489-493, 1996

    Google Scholar 

  21. Liu TJ, Zhang WW, Taylor DL, Roth JA, Goepfert H, Clayman GL: Growth suppression of human head and neck cancer cells by the introduction of a wild-type p53 gene via a recombinant adenovirus. Cancer Res 54: 3662-3667, 1994

    Google Scholar 

  22. Schumacher G, Bruckheimer EM, Beham AW, Honda T, Brisbay S, Roth JA, Logothetis C, McDonnell TJ: Molecular determinants of cell death induction following adenovirusmediated gene transfer of wild-type p53 in prostate cancer cells. Int J Cancer 91: 159-166, 2001

    Google Scholar 

  23. Spitz FR, Nguyen D, Skibber JM, Meyn RE, Cristiano RJ, Roth JA: Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation. Clin. Cancer Res. 2: 1665-1671, 1996

    Google Scholar 

  24. Swisher SG, Roth JA, Nemunaitis J, Lawrence DD, Kemp BL, Carrasco CH, Connors DG, El-Naggar AK, Fossella F, Glisson BS, Hong WK, Khuri FR, Kurie JM, Lee JJ, Lee JS, Mack M, Merritt JA, Nguyen DM, Nesbitt JC, Perez-Soler R, Pisters KM, Putnam JB, Jr, Richli WR, Savin M, Schrump DS, Shin DM, Shulkin A, Walsh GL, Wait J, Weill D, Waugh MKA: Adenovirusmediated p53 gene transfer in advanced non-small-cell lung cancer. J Natl Cancer Inst 91: 763-771, 1999

    Google Scholar 

  25. Schuler M, Rochlitz C, Horowitz JA, Schlegel J, Perruchoud AP, Kommoss F, Bolliger CT, Kauczor HU, Dalquen P, Fritz MA, Swanson S, Herrmann R, Huber C: A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer. Hum Gene Ther 9: 2075-2082, 1998

    Google Scholar 

  26. Schuler M, Herrmann R, De Greve JL, Stewart AK, Gatzemeier U, Stewart DJ, Laufman L, Gralla R, Kuball J, Buhl R, Heussel CP, Kommoss F, Perruchoud AP, Shepherd FA, Fritz MA, Horowitz JA, Huber C, Rochlitz C: Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-smallcell lung cancer: results of a multicenter phase II study. J Clin Oncol 19: 1750-1758, 2001

    Google Scholar 

  27. Nemunaitis J, Swisher SG, Timmons T, Connors D, Mack M, Doerksen L, Weill D, Wait J, Lawrence DD, Kemp BL, Fossella F, Glisson BS, Hong WK, Khuri FR, Kurie JM, Lee JJ, Lee JS, Nguyen DM, Nesbitt JC, Perez-Soler R, Pisters KM, Putnam JB, Richli WR, Shin DM, Walsh GL, Merritt J, Roth J: Adenovirusmediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. J Clin Oncol 18: 609-622, 2000

    Google Scholar 

  28. Weill D, Mack M, Roth J, Swisher S, Proksch S, Merritt J, Nemunaitis J: Adenoviral-mediated p53 gene transfer to non-small cell lung cancer through endobronchial injection. Chest 118: 966-970, 2000

    Google Scholar 

  29. Clayman GL, el-Naggar AK, Lippman SM, Henderson YC, Frederick M, Merritt JA, Zumstein LA, Timmons TM, Liu TJ, Ginsberg L, Roth JA, Hong WK, Bruso P, Goepfert H: Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma. J Clin Oncol 16: 2221-2232, 1998

    Google Scholar 

  30. Clayman GL, Frank DK, Bruso PA, Goepfert H: Adenovirus-mediated wild-type p53 gene transfer as a surgical adjuvant in advanced head and neck cancers. Clin Cancer Res 5: 1715-1722, 1999

    Google Scholar 

  31. Kuball J, Wen SF, Leissner J, Atkins D, Meinhardt P, Quijano E, Engler H, Hutchins B, Maneval DC, G race MJ, Fritz MA, Storkel S, Thuroff JW, Huber C, Schuler M: Successful adenovirus-mediated wild-type p53 gene transfer in patients with bladder cancer by intravesical vector instillation. J Clin Oncol 20: 957-965, 2002

    Google Scholar 

  32. Buller RE, Runnebaum IB, Karlan BY, Horowitz JA, Shahin M, Buekers T, Petrauskas S, Kreienberg R, Slamon D, Pegram M: A phase I/II trial of rAd/p53 (SCH58500) gene replacement in recurrent ovarian cancer. Cancer Gene Ther 9: 553-566, 2002

    Google Scholar 

  33. Dummer R, Bergh J, Karlsson Y, Horowitz JA, Mulder NH, Huinink DTB, Burg G, Hofbauer G, Osanto S: Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors. Cancer Gene Ther 7: 1069-1076, 2000

    Google Scholar 

  34. Lang FF, Yung WKA, Sawaya R, Stephens LC, Tofilon PJ: Adenovirus-mediated p53 gene therapy for human gliomas. Neurosurgery 45: 1093-1104, 1999

    Google Scholar 

  35. Bogler O, Huang H-JS, Kleihues P, Cavenee WK: The p53 gene and its role in human brain tumors. Glia 15: 308-327, 1995

    Google Scholar 

  36. Frankel RH, Bayona W, Koslow M, Newcomb EW: p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res 52: 1427-1433, 1992

    Google Scholar 

  37. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B: Mutations in the p53 gene occur in diverse human tumour types. Nature 342: 705-708, 1989

    Google Scholar 

  38. Kamijo T, Weber JD, Zambetti G, Zindy F, Roussel MF, Sherr CJ: Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci USA 95: 8292-8297, 1998

    Google Scholar 

  39. Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H: Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 150: 1-13, 1997

    Google Scholar 

  40. Kock H, Harris MP, Anderson SC, Machemer T, Hancock W, Sutjipto S, Wills KN, Gregory RJ, Shepard HM, Westphal M, Maneval DC: Adenovirusmediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo. Int. J. Cancer 67: 808-815, 1996

    Google Scholar 

  41. Lang FF, Yung WKA, Raju U, Libunao F, Terry NHA, Tofilon PJ: Enhancement of radiosensitivity of wild-type p53 human glioma cells by adenovirus-mediated delivery of the p53 gene. J Neurosurg 89: 125-132, 1998

    Google Scholar 

  42. Gomez-Manzano C, Fueyo J, Kyritsis AP, Steck PA, Roth JA, McDonnell TJ, Steck KD, Levin VA, Yung WKA: Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res 56: 694-699, 1996

    Google Scholar 

  43. Gomez-Manzano C, Fueyo J, Kyritsis AP, McDonnell TJ, Steck PA, Levin VA, Yung WK: Characterization of p53 and p21 functional interactions in glioma cells en route to apoptosis. J Natl Cancer Inst 89: 1036-1044, 1997

    Google Scholar 

  44. Li H, Alonso-Vanegas M, Colicos MA, Jung SS, Lochmuller H, Sadikot AF, Snipes GJ, Seth P, Karpati G, Nalbantoglu J: Intracerebral adenovirus-mediated p53 tumor suppressor gene therapy for experimental human glioma. Clin Cancer Res 5: 637-642, 1999

    Google Scholar 

  45. Shono T, Tofilon PJ, Schaefer TS, Parikh D, Liu TJ, Lang FF: Apoptosis induced by adenovirus-mediated p53 gene transfer in human glioma correlates with site-specific phosphorylation. Cancer Res 62: 1069-1076, 2002

    Google Scholar 

  46. Badie B, Drazan KE, Kramar MH, Shaked A, Black KL: Adenovirus-mediated p53 gene delivery inhibits 9L glioma growth in rats. Neurol Res 17: 209-216, 1995

    Google Scholar 

  47. Gallardo D, Drazan KE, McBride WH: Adenovirus-based transfer of wild-type p53 gene increases ovarian tumor radiosensitivity. Cancer Res 56: 4891-4893, 1996

    Google Scholar 

  48. Lang FF, Bruner JM, Fuller GN, Aldape K, Prados MD, Chang S, Berger MS, McDermott MW, Kunwar SM, Junck LR, Chandler W, Zwiebel JA, Kaplan RS, Yung WK. Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J. Clin. Oncol. 21: 2508-2518, 2003

    Google Scholar 

  49. Lang FF, Gilbert MR, Puduvalli VK, Weinberg J, Levin VA, Yung WK, Sawaya R, Fuller GN, Conrad CA: Toward better early-phase brain tumor clinical trials: a reappraisal of current methods and proposals for future strategies. Neuro-Oncol 4: 268-277, 2002

    Google Scholar 

  50. Kelly PJ, Daumas-Duport C, Scheithauer BW, Kall BA, Kispert DB: Stereotactic histologic correlations of computed tomography-and magnetic resonance imagingdefined abnormalities in patients with glial neoplasms. Mayo Clin Proc 62: 450-459, 1987

    Google Scholar 

  51. Kelly PJ, Daumas-Duport C, Kispert DB, Kall BA, Scheithauer BW, Illig JJ: Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg 66: 865-874, 1987

    Google Scholar 

  52. Martuza RL: Conditionally replicating herpes vectors for cancer therapy. J Clin Invest 105: 841-846, 2000

    Google Scholar 

  53. Alemany R, Balague C, Curiel DT: Replicative adenoviruses for cancer therapy. Natl Biotechnol 18: 723-727, 2000

    Google Scholar 

  54. Smith R, Huebner RS, Row WP, Schatten WE, Thomas LB: Studies on the use of viruses in the treatment of carcinoma of cervix. Cancer 9: 1211-1218, 1956

    Google Scholar 

  55. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274: 373-376, 1996

    Google Scholar 

  56. Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WK, Kyritsis AP: Amu tant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19: 2-12, 2000

    Google Scholar 

  57. Bergmann M, Romirer I, Sachet M, Fleischhacker R, Garcia-Sastre A, Palese P, Wolff K, Pehamberger H, Jakesz R, Muster T:A genetically engineered influenza A virus with Ras-dependent oncolytic properties. Cancer Res 61: 8188-8193, 2001

    Google Scholar 

  58. Phuangsab A, Lorence RM, Reichard KW, Peeples ME, Walter RJ: Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett 172: 27-36, 2001

    Google Scholar 

  59. Gromeier M, Lachmann S, Rosenfeld MR, Gutin PH, Wimmer E: Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc Natl Acad Sci USA 97: 6803-6808, 2000

    Google Scholar 

  60. Strong JE, Coffey MC, Tang D, Sabinin P, Lee PW: The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. Embo J 17: 3351-3362, 1998

    Google Scholar 

  61. Timiryasova TM, Li J, Chen B, Chong D, Langridge WH, Gridley DS, Fodor I: Antitumor effect of vaccinia virus in glioma model. Oncol Res 11: 133-144, 1999

    Google Scholar 

  62. Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC: Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Natl Med 6: 821-825, 2000

    Google Scholar 

  63. Curiel DT: The development of conditionally replicative adenoviruses for cancer therapy. Clin Cancer Res 6: 3395-3399, 2000

    Google Scholar 

  64. Reid T, Galanis E, Abbruzzese J, Sze D, Andrews J, Romel L, Hatfield M, Rubin J, Kirn D: 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, 2001

    Google Scholar 

  65. Ganly I, Kirn D, Eckhardt G, Rodriguez GI, Soutar DS, Otto R, Robertson AG, Park O, Gulley ML, Heise C, Von Hoff DD, Kaye SB, Eckhardt SG: A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res 6: 798-806, 2000

    Google Scholar 

  66. Nemunaitis J, Ganly I, Khuri F, Arseneau J, Kuhn J, McCarty T, Landers S, Maples P, Romel L, Randlev B, Reid T, Kaye S, Kirn D: Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD genedeleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. Cancer Res 60: 6359-6366, 2000

    Google Scholar 

  67. Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C, Randlev B, Gillenwater AM, Bruso P, Kaye SB, Hong WK, Kirn DH: A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Natl Med 6: 879-885, 2000

    Google Scholar 

  68. Lamont JP, Nemunaitis J, Kuhn JA, Landers SA, McCarty TM: A prospective phase II trial of ONYX-015 adenovirus and chemotherapy in recurrent squamous cell carcinoma of the head and neck (the Baylor experience). Ann Surg Oncol 7: 588-592, 2000

    Google Scholar 

  69. Habib NA, Sarraf CE, Mitry RR, Havlik R, Nicholls J, Kelly M, Vernon CC, Gueret-Wardle D, El-Masry R, Salama H, Ahmed R, Michail N, Edward E, Jensen SL: E1Bdeleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors. Hum Gene Ther 12: 219-226, 2001

    Google Scholar 

  70. Habib N, Salama H, Abd El LatifAbu Median A, Isac Anis I, Abd Al Aziz RA, Sarraf C, Mitry R, Havlik R, Seth P, Hartwigsen J, Bhushan R, Nicholls J, Jensen S: Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma. Cancer Gene Ther 9: 254-259, 2002

    Google Scholar 

  71. Nemunaitis J, Cunningham C, Buchanan A, Blackburn A, Edelman G, Maples P, Netto G, Tong A, Randlev B, Olson S, Kirn D: Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther 8: 746-759, 2001

    Google Scholar 

  72. Vasey PA, Shulman LN, Campos S, Davis J, Gore M, Johnston S, Kirn DH, O'Neill V, Siddiqui N, Seiden MV, Kaye SB: Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer. J Clin Oncol 20: 1562-1569, 2002

    Google Scholar 

  73. Mulvihill S, Warren R, Venook A, Adler A, Randlev B, Heise C, Kirn D: Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial. Gene Ther 8: 308-315, 2001

    Google Scholar 

  74. Suzuki K, Fueyo J, Krasnykh V, Reynolds PN, Curiel DT, Alemany R: A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res 7: 120-126, 2001

    Google Scholar 

  75. Fueyo J, Alemany R, Gomez-Manzano C, Fuller GN, Khan A, Conrad CA, Liu TJ, Jiang H, Lemoine M, Suzuki K, Sawaya R, Currier MA, Yung W, Lang FF: Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the Rb pathway. J Natl Cancer Inst 95: 652-60, 2003

    Google Scholar 

  76. Bauerschmitz GJ, Lam JT, Kanerva A, Suzuki K, Nettelbeck DM, Dmitriev I, Krasnykh V, Mikheeva GV, Barnes MN, Alvarez RD, Dall P, Alemany R, Curiel DT, Hemminki A: Treatment of ovarian cancer with a tropism modified oncolytic adenovirus. Cancer Res 62: 1266-1270, 2002

    Google Scholar 

  77. Cripe TP, Dunphy EJ, Holub AD, Saini A, Vasi NH, Mahller YY, Collins MH, Snyder JD, Krasnykh V, Curiel DT, Wickham TJ, DeGregori J, Bergelson JM, Currier MA: Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells. Cancer Res 61: 2953-2960, 2001

    Google Scholar 

  78. Balague C, Noya F, Alemany R, Chow LT, Curiel DT: Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes. J Virol 75: 7602-7611, 2001

    Google Scholar 

  79. Lamfers ML, Grill J, Dirven CM, Van Beusechem VW, Geoerger B, Van Den Berg J, Alemany R, Fueyo J, Curiel DT, Vassal G, Pinedo HM, Vandertop WP, Gerritsen WR: Potential of the conditionally replicative adenovirus Ad5-Delta24RGD in the treatment of malignant gliomas and its enhanced effect with radiotherapy. Cancer Res 62: 5736-5742, 2002

    Google Scholar 

  80. van Beusechem VW, van den Doel PB, Grill J, Pinedo HM, Gerritsen WR: Conditionally replicative adenovirus expressing p53 exhibits enhanced oncolytic potency. Cancer Res 62: 6165-6171, 2002

    Google Scholar 

  81. Wildner O, Morris JC, Vahanian NN, Ford H Jr, Ramsey WJ, Blaese RM: Adenoviral vectors capable of replication improve the efficacy of HSVtk/GCV suicide gene therapy of cancer. Gene Ther 6: 57-62, 1999

    Google Scholar 

  82. Wildner O, Blaese RM, Morris JC: Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase. Cancer Res 59: 410-413, 1999

    Google Scholar 

  83. Wildner O, Morris JC: Therapy of peritoneal carcinomatosis from colon cancer with oncolytic adenoviruses. J Gene Med 2: 353-360, 2000

    Google Scholar 

  84. Lambright ES, Amin K, Wiewrodt R, Force SD, Lanuti M, Propert KJ, Litzky L, Kaiser LR, Albelda SM: Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy. Gene Ther 8: 946-953, 2001

    Google Scholar 

  85. Rogulski KR, Wing MS, Paielli DL, Gilbert JD, Kim JH, Freytag SO: Double suicide gene therapy augments the antitumor activity of a replication-competent lytic adenovirus through enhanced cytotoxicity and radiosensitization. Hum Gene Ther 11: 67-76, 2000

    Google Scholar 

  86. Freytag SO, Rogulski KR, Paielli DL, Gilbert JD, Kim JH: A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. Hum Gene Ther 9: 1323-1333, 1998

    Google Scholar 

  87. Morris JC, Wildner O: Therapy of head and neck squamous cell carcinoma with an oncolytic adenovirus expressing HSV-tk. Mol Ther 1: 56-62, 2000

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Giacomo G. Vecil & Frederick F. Lang

Authors
  1. Giacomo G. Vecil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frederick F. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vecil, G.G., Lang, F.F. Clinical Trials of Adenoviruses in Brain Tumors: A Review of Ad-p53 and Oncolytic Adenoviruses. J Neurooncol 65, 237–246 (2003). https://doi.org/10.1023/B:NEON.0000003653.45635.32

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEON.0000003653.45635.32

Search

Navigation