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Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment

Cancer Gene Therapy volume 14, pages 627–639 (2007)Cite this article

Abstract

In this study we compared side-by-side the anti-neoplastic activity of the oncolytic herpes simplex virus-1 (HSV-1) vector G47Δ with that of a conditionally replicative adenoviral vector for the treatment of glioblastoma. We analyzed the transduction efficiency of permanent glioblastoma cell lines and short-term cultures of glioblastoma cells with HSV.Luc and four adenovirus type 5 (Ad5)-based vectors that differed only in their fiber gene (Ad5.Luc, AdlucRGD, and the fiber chimeric vectors Ad5/3.Luc and Ad5/35.Luc). In the tested short-term cultures of glioblastoma cells the vectors Ad5/35.Luc and HSV.Luc had an equal transduction efficiency which was ∼70% higher than that of Ad5.Luc. In a subcutaneous xenograft glioblastoma model in nude mice we observed a significantly higher local tumor control with the G47Δ vector compared to the conditionally replicative Ad5/35 adenovirus. We confirmed in glioblastoma that the intratumoral expression of measles virus fusogenic membrane glycoproteins (FMG) encoded by replication-defective Ad5/35 or HSV-1 amplicon vectors synergistically enhances chemotherapy with temozolomide. The anti-neoplastic effect was superior when the replication-defective FMG encoding vectors were trans-complemented for replication with the respective oncolytic vector. This approach was necessary due to packaging constraints of adenovirus. At day 100, of 6 treated animals 1 was alive that received the Ad5/35- and 3 that received the HSV-1-based triple therapy. In an intracranial glioblastoma xenograft model we demonstrated the applicability of this strategy. Due to the higher oncolytic efficacy and packaging capacity of the HSV-1 vectors compared to adenovirus, these vectors are promising for the treatment of glioblastoma.

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References

  1. Castro MG, Cowen R, Williamson IK, David A, Jimenez-Dalmaroni MJ, Yuan X et al. Current and future strategies for the treatment of malignant brain tumors. Pharmacol Ther 2003; 98: 71–108.

    Article  CAS  PubMed  Google Scholar 

  2. Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM . Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 1991; 252: 854–856.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Chou J, Kern ER, Whitley RJ, Roizman B . Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science 1990; 250: 1262–1266.

    Article  CAS  PubMed  Google Scholar 

  5. Goldstein DJ, Weller SK . Herpes simplex virus type 1-induced ribonucleotide reductase activity is dispensable for virus growth and DNA synthesis: isolation and characterization of an ICP6 lacZ insertion mutant. J Virol 1988; 62: 196–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 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 Ther 2000; 7: 867–874.

    Article  CAS  PubMed  Google Scholar 

  7. 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 Ther 2000; 7: 859–866.

    Article  CAS  PubMed  Google Scholar 

  8. Smith RR, Huebner RJ, Rowe WP, Schatten WE, Thomas LB . Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 1956; 9: 1211–1218.

    Article  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996; 274: 373–376.

    Article  CAS  PubMed  Google Scholar 

  11. Hall AR, Dix BR, O'Carroll SJ, Braithwaite AW . p53-dependent cell death/apoptosis is required for a productive adenovirus infection. Nat Med 1998; 4: 1068–1072.

    Article  CAS  PubMed  Google Scholar 

  12. Rothmann T, Hengstermann A, Whitaker NJ, Scheffner M, zur HH . Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells. J Virol 1998; 72: 9470–9478.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Goodrum FD, Ornelles DA . p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection. J Virol 1998; 72: 9479–9490.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Turnell AS, Grand RJ, Gallimore PH . The replicative capacities of large E1B-null group A and group C adenoviruses are independent of host cell p53 status. J Virol 1999; 73: 2074–2083.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Harada JN, Berk AJ . p53-Independent and -dependent requirements for E1B-55K in adenovirus type 5 replication. J Virol 1999; 73: 5333–5344.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Hay JG, Shapiro N, Sauthoff H, Heitner S, Phupakdi W, Rom WN . Targeting the replication of adenoviral gene therapy vectors to lung cancer cells: the importance of the adenoviral E1b-55 kD gene. Hum Gene Ther 1999; 10: 579–590.

    Article  CAS  PubMed  Google Scholar 

  17. Wildner O, Morris JC . The Role of the E1B 55 kDa gene in oncolytic adenoviral vectors expressing HSV-tk: assessment of anti-tumor efficacy and toxicity. Cancer Res 2000; 60: 4167–4174.

    CAS  PubMed  Google Scholar 

  18. Kirn D . Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned? Gene Ther 2001; 8: 89–98.

    Article  CAS  PubMed  Google Scholar 

  19. Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L et al. 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. Nat Med 2000; 6: 879–885.

    Article  CAS  PubMed  Google Scholar 

  20. Heise C, Lemmon M, Kirn D . Efficacy with a replication-selective adenovirus plus cisplatin-based chemotherapy: dependence on sequencing but not p53 functional status or route of administration. Clin Cancer Res 2000; 6: 4908–4914.

    CAS  PubMed  Google Scholar 

  21. Nemunaitis J, Khuri F, Ganly I, Arseneau J, Posner M, Vokes E et al. Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol 2001; 19: 289–298.

    Article  CAS  PubMed  Google Scholar 

  22. Wein LM, Wu JT, Kirn DH . Validation and analysis of a mathematical model of a replication-competent oncolytic virus for cancer treatment: implications for virus design and delivery. Cancer Res 2003; 63: 1317–1324.

    CAS  PubMed  Google Scholar 

  23. Todo T, Martuza RL, Rabkin SD, Johnson PA . Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci USA 2001; 98: 6396–6401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Scholzen T, Gerdes J . The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000; 182: 311–322.

    Article  CAS  PubMed  Google Scholar 

  25. Fuerer C, Iggo R . Adenoviruses with Tcf binding sites in multiple early promoters show enhanced selectivity for tumour cells with constitutive activation of the wnt signalling pathway. Gene Ther 2002; 9: 270–281.

    Article  CAS  PubMed  Google Scholar 

  26. Hernandez-Alcoceba R, Pihalja M, Qian D, Clarke MF . New oncolytic adenoviruses with hypoxia- and estrogen receptor-regulated replication. Hum Gene Ther 2002; 13: 1737–1750.

    Article  CAS  PubMed  Google Scholar 

  27. Johnson L, Shen A, Boyle L, Kunich J, Pandey K, Lemmon M et al. Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents. Cancer Cell 2002; 1: 325–337.

    Article  CAS  PubMed  Google Scholar 

  28. Banerjee NS, Rivera AA, Wang M, Chow LT, Broker TR, Curiel DT et al. Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/promoter-driven E1A, E4, or both in submerged cells and organotypic cultures. Mol Cancer Ther 2004; 3: 437–449.

    CAS  PubMed  Google Scholar 

  29. Li X, Zhang YP, Kim HS, Bae KH, Stantz KM, Lee SJ et al. Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer. Cancer Res 2005; 65: 1941–1951.

    Article  CAS  PubMed  Google Scholar 

  30. Hoffmann D, Wildner O . Restriction of adenoviral replication to the transcriptional intersection of two different promoters for colorectal and pancreatic cancer treatment. Mol Cancer Ther 2006; 5: 1–8.

    Google Scholar 

  31. Li Y, Pong RC, Bergelson JM, Hall MC, Sagalowsky AI, Tseng CP et al. Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy. Cancer Res 1999; 59: 325–330.

    CAS  PubMed  Google Scholar 

  32. Douglas JT, Kim M, Sumerel LA, Carey DE, Curiel DT . Efficient oncolysis by a replicating adenovirus (ad) in vivo is critically dependent on tumor expression of primary ad receptors. Cancer Res 2001; 61: 813–817.

    CAS  PubMed  Google Scholar 

  33. Fuxe J, Liu L, Malin S, Philipson L, Collins VP, Pettersson RF . Expression of the coxsackie and adenovirus receptor in human astrocytic tumors and xenografts. Int J Cancer 2003; 103: 723–729.

    Article  CAS  PubMed  Google Scholar 

  34. Asaoka K, Tada M, Sawamura Y, Ikeda J, Abe H . Dependence of efficient adenoviral gene delivery in malignant glioma cells on the expression levels of the Coxsackievirus and adenovirus receptor. Journal of Neurosurgery 2000; 92: 1002–1008.

    Article  CAS  PubMed  Google Scholar 

  35. Lamfers ML, Grill J, Dirven CM, Van BV, Geoerger B, Van Den BJ et al. Potential of the conditionally replicative adenovirus Ad5-Delta24RGD in the treatment of malignant gliomas and its enhanced effect with radiotherapy. Cancer Res 2002; 62: 5736–5742.

    CAS  PubMed  Google Scholar 

  36. Shinoura N, Yoshida Y, Tsunoda R, Ohashi M, Zhang W, Asai A et al. Highly augmented cytopathic effect of a fiber-mutant E1B-defective adenovirus for gene therapy of gliomas. Cancer Res 1999; 59: 3411–3416.

    CAS  PubMed  Google Scholar 

  37. Taki M, Kagawa S, Nishizaki M, Mizuguchi H, Hayakawa T, Kyo S et al. Enhanced oncolysis by a tropism-modified telomerase-specific replication-selective adenoviral agent OBP-405 (‘Telomelysin-RGD’). Oncogene 2005; 24: 3130–3140.

    Article  CAS  PubMed  Google Scholar 

  38. Gaggar A, Shayakhmetov DM, Lieber A . CD46 is a cellular receptor for group B adenoviruses. Nat Med 2003; 9: 1408–1412.

    Article  CAS  PubMed  Google Scholar 

  39. Marttila M, Persson D, Gustafsson D, Liszewski MK, Atkinson JP, Wadell G et al. CD46 is a cellular receptor for all species B adenoviruses except types 3 and 7. J Virol 2005; 79: 14429–14436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ulasov IV, Tyler MA, Zheng S, Han Y, Lesniak MS . CD46 represents a target for adenoviral gene therapy of malignant glioma. Hum Gene Ther 2006; 17: 556–564.

    Article  CAS  PubMed  Google Scholar 

  41. Bateman A, Bullough F, Murphy S, Emiliusen L, Lavillette D, Cosset FL et al. Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Res 2000; 60: 1492–1497.

    CAS  PubMed  Google Scholar 

  42. Galanis E, Bateman A, Johnson K, Diaz RM, James CD, Vile R et al. Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas. Hum Gene Ther 2001; 12: 811–821.

    Article  CAS  PubMed  Google Scholar 

  43. Fu X, Tao L, Jin A, Vile R, Brenner MK, Zhang X . Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect. Mol Ther 2003; 7: 748–754.

    Article  CAS  PubMed  Google Scholar 

  44. Li H, Haviv YS, Derdeyn CA, Lam J, Coolidge C, Hunter E et al. Human immunodeficiency virus type 1-mediated syncytium formation is compatible with adenovirus replication and facilitates efficient dispersion of viral gene products and de novo-synthesized virus particles. Hum Gene Ther 2001; 12: 2155–2165.

    Article  CAS  PubMed  Google Scholar 

  45. Linardakis E, Bateman A, Phan V, Ahmed A, Gough M, Olivier K et al. Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion. Cancer Res 2002; 62: 5495–5504.

    CAS  PubMed  Google Scholar 

  46. Errington F, Bateman A, Kottke T, Thompson J, Harrington K, Merrick A et al. Allogeneic tumor cells expressing fusogenic membrane glycoproteins as a platform for clinical cancer immunotherapy. Clin Cancer Res 2006; 12: 1333–1341.

    Article  CAS  PubMed  Google Scholar 

  47. Ahmed A, Jevremovic D, Suzuki K, Kottke T, Thompson J, Emery S et al. Intratumoral expression of a fusogenic membrane glycoprotein enhances the efficacy of replicating adenovirus therapy. Gene Ther 2003; 10: 1663–1671.

    Article  CAS  PubMed  Google Scholar 

  48. Nakamura T, Peng KW, Vongpunsawad S, Harvey M, Mizuguchi H, Hayakawa T et al. Antibody-targeted cell fusion. Nat Biotechnol 2004; 22: 331–336.

    Article  CAS  PubMed  Google Scholar 

  49. Hoffmann D, Wildner O . Enhanced killing of pancreatic cancer cells by expression of fusogenic membrane glycoproteins in combination with chemotherapy. Mol Cancer Ther 2006; 5: 2013–2022.

    Article  CAS  PubMed  Google Scholar 

  50. Hoffmann D, Bangen JM, Bayer W, Wildner O . Synergy between expression of fusogenic membrane proteins, chemotherapy and facultative virotherapy in colorectal cancer. Gene Ther 2006; 13: 1534–1544.

    Article  CAS  PubMed  Google Scholar 

  51. Bett AJ, Prevec L, Graham FL . Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 1993; 67: 5911–5921.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Dion LD, Goldsmith KT, Strong TV, Bilbao G, Curiel DT, Garver RIJ . E1A RNA transcripts amplify adenovirus-mediated tumor reduction. Gene Ther 1996; 3: 1021–1025.

    CAS  PubMed  Google Scholar 

  53. 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 1998; 9: 1323–1333.

    Article  CAS  PubMed  Google Scholar 

  54. Alemany R, Lai S, Lou YC, Jan HY, Fang X, Zhang WW . Complementary adenoviral vectors for oncolysis. Cancer Gene Ther 1999; 6: 21–25.

    Article  CAS  PubMed  Google Scholar 

  55. Wildner O, Blaese RM, Candotti F . Enzyme prodrug gene therapy: synergistic use of the herpes simplex virus-cellular thymidine kinase/ganciclovir system and thymidylate synthase inhibitors for the treatment of colon cancer. Cancer Res 1999; 59: 5233–5238.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  57. Wolkersdorfer GW, Morris JC, Ehninger G, Ramsey WJ . Trans-complementing adenoviral vectors for oncolytic therapy of malignant melanoma. J Gene Med 2004; 6: 652–662.

    Article  CAS  PubMed  Google Scholar 

  58. Lee CT, Park KH, Yanagisawa K, Adachi Y, Ohm JE, Nadaf S et al. Combination therapy with conditionally replicating adenovirus and replication defective adenovirus. Cancer Res 2004; 64: 6660–6665.

    Article  CAS  PubMed  Google Scholar 

  59. Besnard F, Brenner M, Nakatani Y, Chao R, Purohit HJ, Freese E . Multiple interacting sites regulate astrocyte-specific transcription of the human gene for glial fibrillary acidic protein. J Biol Chem 1991; 266: 18877–18883.

    CAS  PubMed  Google Scholar 

  60. Hoffmann D, Wildner O . Efficient generation of double heterologous promoter controlled oncolytic adenovirus vectors by a single homologous recombination step in Escherichia coli. BMC Biotechnol 2006; 6: 36.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Nilsson M, Ljungberg J, Richter J, Kiefer T, Magnusson M, Lieber A et al. Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. J Gene Med 2004; 6: 631–641.

    Article  CAS  PubMed  Google Scholar 

  62. Dmitriev I, Krasnykh V, Miller CR, Wang M, Kashentseva E, Mikheeva G et al. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol 1998; 72: 9706–9713.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. He TC, Zhou S, da Costa LT, Yu J, Kinzler KW, Vogelstein B . A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci USA 1998; 95: 2509–2514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Horn GP, Vongpunsawad S, Kornmann E, Fritz B, Dittmer DP, Cattaneo R et al. Enhanced cytotoxicity without internuclear spread of adenovirus upon cell fusion by measles virus glycoproteins. J Virol 2005; 79: 1911–1917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Morris JC, Wildner O . Therapy of head and neck squamous cell carcinoma with an oncolytic adenovirus expressing HSV-tk. Molecular Therapy 2000; 1: 56–62.

    Article  CAS  PubMed  Google Scholar 

  66. Mittereder N, March KL, Trapnell BC . Evaluation of the concentration and bioactivity of adenovirus vectors for gene therapy. J Virol 1996; 70: 7498–7509.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Horikawa I, Cable PL, Afshari C, Barrett JC . Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res 1999; 59: 826–830.

    CAS  PubMed  Google Scholar 

  68. Chou TC, Talalay P . Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27–55.

    Article  CAS  PubMed  Google Scholar 

  69. Chou J, Chou TC . Quantification of synergism and antagonism of two or more drugs by computerized analysis. In: Chou TC, Rideout DC (eds) Synergism and Antagonism in Chemotherapy. Academic Press: San Diego, CA, 1991, pp 223–244.

    Google Scholar 

  70. Pincus S, Robertson W, Rekosh D . Characterization of the effect of aphidicolin on adenovirus DNA replication: evidence in support of a protein primer model of initiation. Nucleic Acids Res 1981; 9: 4919–4938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hoffmann D, Jogler C, Wildner O . Effects of the Ad5 upstream E1 region and gene products on heterologous promoters. J Gene Med 2005; 7: 1356–1366.

    Article  CAS  PubMed  Google Scholar 

  72. Burrows J, Nitsche A, Bayly B, Walker E, Higgins G, Kok T . Detection and subtyping of Herpes simplex virus in clinical samples by LightCycler PCR, enzyme immunoassay and cell culture. BMC Microbiol 2002; 2: 12.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Short JJ, Pereboev AV, Kawakami Y, Vasu C, Holterman MJ, Curiel DT . Adenovirus serotype 3 utilizes CD80 (B7.1) and CD86 (B7.2) as cellular attachment receptors. Virology 2004; 322: 349–359.

    Article  CAS  PubMed  Google Scholar 

  74. Shayakhmetov DM, Papayannopoulou T, Stamatoyannopoulos G, Lieber A . Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector. J Virol 2000; 74: 2567–2583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hitt MM, Graham FL . Adenovirus E1A under the control of heterologous promoters: wide variation in E1A expression levels has little effect on virus replication. Virology 1990; 179: 667–678.

    Article  CAS  PubMed  Google Scholar 

  76. Kelly Jr TJ, Lewis Jr AM . Use of nondefective adenovirus-simian virus 40 hybrids for mapping the simian virus 40 genome. J Virol 1973; 12: 643–652.

    PubMed  PubMed Central  Google Scholar 

  77. Tollefson AE, Scaria A, Hermiston TW, Ryerse JS, Wold LJ, Wold WS . The adenovirus death protein (E3–11.6 K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells. J Virol 1996; 70: 2296–2306.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Yant SR, Ehrhardt A, Mikkelsen JG, Meuse L, Pham T, Kay MA . Transposition from a gutless adeno-transposon vector stabilizes transgene expression in vivo. Nat Biotechnol 2002; 20: 999–1005.

    Article  CAS  PubMed  Google Scholar 

  79. Aghi M, Rabkin S, Martuza RL . Effect of chemotherapy-induced DNA repair on oncolytic herpes simplex viral replication. J Natl Cancer Inst 2006; 98: 38–50.

    Article  CAS  PubMed  Google Scholar 

  80. Hoffmann D, Grunwald T, Kuate S, Wildner O . Mechanistic analysis and comparison of viral fusogenic membrane proteins for their synergistic effects on chemotherapy. Cancer Biol Ther 2007; 6 [Epub ahead of print].

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to Samuel Rabkin (Mol Neurosurg Lab, Massachusetts General Hospital, Charlestown, MA) for kindly providing G47Δ, Yoshinaga Saeki (Department of Neurological Surgery, The Ohio State University, OH) for giving the HSV-1-BAC clone fHSVΔpacΔ27Δkn, Cornell Fraefel (University of Zurich, Switzerland) for kindly providing the HSV amplicon plasmid vector pHSVPrPUC, Izumi Horikawa (NCI, National Institutes of Health, Bethesda, MD) for the hTERT promoter, Michael Brenner (UAB, Birmingham, AL) for the hGFAP promoter, Rozanne Sandri-Goldin (Department of Microbiology and Molecular Genetics, University of California, Irvine, CA) for the Vero 2-2 cells and Roberto Cattaneo (Molecular Medicine Program, Mayo Clinic Rochester, MN) for giving the measles virus H and F bicistronic expression plasmid pGC-H/IRES/F. In addition, we thank David T Curiel (Gene Therapy Center, The University of Alabama at Birmingham) for providing the vectors Ad5.Luc, Ad5/3.Luc and Ad5lucRGD, and Xiaolong Fan (Lund University, Lund, Sweden) for providing pAdEasy-1/F35. Furthermore, we thank Bernhard Meyer (Friedrich-Wilhelms-University Bonn, Department of Neurosurgery, Germany) for providing tumor specimens. The authors would like to thank Klaus Überla for providing constant support, Cathrin Walter (West German Cancer Center, University of Essen, Germany) and Wibke Bayer for critical review of this manuscript. Furthermore, we would like to thank André Lieber, University of Washington, Seattle, WA for his support. In addition the authors thank Regina Reszka, MDC Berlin, and Christian Jogler for establishing the intracranial tumor model. This work was supported by grants from Deutsche Forschungsgemeinschaft, Dr Mildred Scheel Stiftung für Krebsforschung, and Forschungsförderung Ruhr-Universität Bochum Medizinische Fakultät (FoRUM) to OW.

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Hoffmann, D., Wildner, O. Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment. Cancer Gene Ther 14, 627–639 (2007). https://doi.org/10.1038/sj.cgt.7701055

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