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Cellular genetic tools to control oncolytic adenoviruses for virotherapy of cancer

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Abstract

Key challenges facing cancer therapy are the development of tumor-specific drugs and the implementation of potent multimodal treatment regimens. Oncolytic adenoviruses, featuring cancer-selective viral cell lysis and spread, constitute a particularly interesting drug platform towards both goals. First, as complex biological agents, adenoviruses allow for rational drug development by genetic incorporation of targeting mechanisms that exert their function at different stages of the viral replication cycle. Secondly, therapeutic genes implementing diverse cancer cell-killing activities can be inserted into the oncolytic adenovirus genome without loss of replication potential, thus deriving a “one-agent combination therapy”. This article reviews an intriguing approach to derive oncolytic adenoviruses, which is to insert cellular genetic regulatory elements into adenovirus genomes for control of virus replication and therapeutic gene expression. This approach has been thoroughly investigated and optimized during the last decade for transcriptional targeting of adenovirus replication and gene expression to a wide panel of tumor types. More recently, further cellular regulatory mechanisms, such as mRNA stability and translation regulation, have been reported as tools for virus control. Consequently, oncolytic adenoviruses with a remarkable specificity profile for prostate cancer, gastrointestinal cancers, liver cancer, breast cancer, lung cancer, melanoma, and other cancers were derived. Such specificity profiles allow for the engineering of new generations of oncolytic adenoviruses with improved potency by enhancing viral cell binding and entry or by expressing therapeutic genes. Clearly, genetic engineering of viruses has great potential for the development of innovative antitumor drugs—towards targeted and multimodal cancer therapy.

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References

  1. Kelly E, Russell SJ (2007) History of oncolytic viruses: genesis to genetic engineering. Mol Ther 15:651–659

    Article  PubMed  CAS  Google Scholar 

  2. Alemany R, Balague C, Curiel DT (2000) Replicative adenoviruses for cancer therapy. Nat Biotechnol 18:723–727

    Article  PubMed  CAS  Google Scholar 

  3. Basak SK, Kiertscher SM, Harui A, Roth MD (2004) Modifying adenoviral vectors for use as gene-based cancer vaccines. Viral Immunol 17:182–196

    Article  PubMed  CAS  Google Scholar 

  4. McConnell MJ, Imperiale MJ (2004) Biology of adenovirus and its use as a vector for gene therapy. Hum Gene Ther 15:1022–1033

    Article  PubMed  CAS  Google Scholar 

  5. Bischoff JR, Kirn DH, Williams A et al (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274:373–376

    Article  PubMed  CAS  Google Scholar 

  6. Lin E, Nemunaitis J (2004) Oncolytic viral therapies. Cancer Gene Ther 11:643–664

    Article  PubMed  CAS  Google Scholar 

  7. Baum C, Schambach A, Bohne J, Galla M (2006) Retrovirus vectors: toward the plentivirus? Mol Ther 13:1050–1063

    Article  PubMed  CAS  Google Scholar 

  8. Hacein-Bey-Abina S, Le Deist F, Carlier F et al (2002) Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med 346:1185–1193

    Article  PubMed  CAS  Google Scholar 

  9. Cavazzana-Calvo M, Fischer A (2007) Gene therapy for severe combined immunodeficiency: are we there yet? J Clin Invest 117:1456–1465

    Article  PubMed  CAS  Google Scholar 

  10. Warrington KH Jr, Herzog RW (2006) Treatment of human disease by adeno-associated viral gene transfer. Hum Genet 119:571–603

    Article  PubMed  CAS  Google Scholar 

  11. Nettelbeck DM, Curiel DT (2003) Tumor-busting viruses. Sci Am 289:68–75

    Article  PubMed  Google Scholar 

  12. O’Shea CC (2005) Viruses—seeking and destroying the tumor program. Oncogene 24:7640–7655

    Article  PubMed  CAS  Google Scholar 

  13. Fueyo J, Gomez MC, Alemany R et al (2000) A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19:2–12

    Article  PubMed  CAS  Google Scholar 

  14. Heise C, Hermiston T, Johnson L et al (2000) An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 6:1134–1139

    Article  PubMed  CAS  Google Scholar 

  15. O’Shea CC, Johnson L, Bagus B et al (2004) Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell 6:611–623

    Article  PubMed  CAS  Google Scholar 

  16. Cascallo M, Capella G, Mazo A, Alemany R (2003) Ras-dependent oncolysis with an adenovirus VAI mutant. Cancer Res 63:5544–5550

    PubMed  CAS  Google Scholar 

  17. Wang Y, Xue SA, Hallden G et al (2005) Virus-associated RNA I-deleted adenovirus, a potential oncolytic agent targeting EBV-associated tumors. Cancer Res 65:1523–1531

    Article  PubMed  CAS  Google Scholar 

  18. Bieler A, Mantwill K, Dravits T et al (2006) Novel three-pronged strategy to enhance cancer cell killing in glioblastoma cell lines: histone deacetylase inhibitor, chemotherapy, and oncolytic adenovirus dl520. Hum Gene Ther 17:55–70

    Article  PubMed  CAS  Google Scholar 

  19. Nettelbeck DM, Jerome V, Muller R (2000) Gene therapy: designer promoters for tumour targeting. Trends Genet 16:174–181

    Article  PubMed  CAS  Google Scholar 

  20. Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR (1997) Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res 57:2559–2563

    PubMed  CAS  Google Scholar 

  21. Nettelbeck DM, Rivera AA, Balague C, Alemany R, Curiel DT (2002) Novel oncolytic adenoviruses targeted to melanoma: specific viral replication and cytolysis by expression of E1A mutants from the tyrosinase enhancer/promoter. Cancer Res 62:4663–4670

    PubMed  CAS  Google Scholar 

  22. Bentley NJ, Eisen T, Goding CR (1994) Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator. Mol Cell Biol 14:7996–8006

    PubMed  CAS  Google Scholar 

  23. Ganss R, Montoliu L, Monaghan AP, Schutz G (1994) A cell-specific enhancer far upstream of the mouse tyrosinase gene confers high level and copy number-related expression in transgenic mice. Embo J 13:3083–3093

    PubMed  CAS  Google Scholar 

  24. Kluppel M, Beermann F, Ruppert S, Schmid E, Hummler E, Schutz G (1991) The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina. Proc Natl Acad Sci USA 88:3777–3781

    Article  PubMed  CAS  Google Scholar 

  25. Lowings P, Yavuzer U, Goding CR (1992) Positive and negative elements regulate a melanocyte-specific promoter. Mol Cell Biol 12:3653–3662

    PubMed  CAS  Google Scholar 

  26. Shibata K, Muraosa Y, Tomita Y, Tagami H, Shibahara S (1992) Identification of a cis-acting element that enhances the pigment cell-specific expression of the human tyrosinase gene. J Biol Chem 267:20584–20588

    PubMed  CAS  Google Scholar 

  27. Yavuzer U, Goding CR (1994) Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. Mol Cell Biol 14:3494–3503

    PubMed  CAS  Google Scholar 

  28. Siders WM, Halloran PJ, Fenton RG (1996) Transcriptional targeting of recombinant adenoviruses to human and murine melanoma cells. Cancer Res 56:5638–5646

    PubMed  CAS  Google Scholar 

  29. Vile RG, Hart IR (1993) In vitro and in vivo targeting of gene expression to melanoma cells. Cancer Res 53:962–967

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Yamamoto M, Davydova J, Wang M et al (2003) Infectivity enhanced, cyclooxygenase-2 promoter-based conditionally replicative adenovirus for pancreatic cancer. Gastroenterology 125:1203–1218

    Article  PubMed  CAS  Google Scholar 

  33. Doronin K, Kuppuswamy M, Toth K et al (2001) Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy. J Virol 75:3314–3324

    Article  PubMed  CAS  Google Scholar 

  34. Zhang J, Ramesh N, Chen Y et al (2002) Identification of human uroplakin II promoter and its use in the construction of CG8840, a urothelium-specific adenovirus variant that eliminates established bladder tumors in combination with docetaxel. Cancer Res 62:3743–3750

    PubMed  CAS  Google Scholar 

  35. Huang TG, Savontaus MJ, Shinozaki K, Sauter BV, Woo SL (2003) Telomerase-dependent oncolytic adenovirus for cancer treatment. Gene Ther 10:1241–1247

    Article  PubMed  CAS  Google Scholar 

  36. Johnson L, Shen A, Boyle L et al (2002) Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents. Cancer Cell 1:325–337

    Article  PubMed  CAS  Google Scholar 

  37. Kamizono J, Nagano S, Murofushi Y et al (2005) Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific and efficient viral replication. Cancer Res 65:5284–5291

    Article  PubMed  CAS  Google Scholar 

  38. Wirth T, Zender L, Schulte B et al (2003) A telomerase-dependent conditionally replicating adenovirus for selective treatment of cancer. Cancer Res 63:3181–3188

    PubMed  CAS  Google Scholar 

  39. Hallenbeck PL, Chang YN, Hay C et al (1999) A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma. Hum Gene Ther 10:1721–1733

    Article  PubMed  CAS  Google Scholar 

  40. Post DE, Van Meir EG (2003) A novel hypoxia-inducible factor (HIF) activated oncolytic adenovirus for cancer therapy. Oncogene 22:2065–2072

    Article  PubMed  CAS  Google Scholar 

  41. Toth K, Djeha H, Ying B et al (2004) An oncolytic adenovirus vector combining enhanced cell-to-cell spreading, mediated by the ADP cytolytic protein, with selective replication in cancer cells with deregulated Wnt signaling. Cancer Res 64:3638–3644

    Article  PubMed  CAS  Google Scholar 

  42. Li X, Zhang YP, Kim HS et al (2005) Gene therapy for prostate cancer by controlling adenovirus E1a and E4 gene expression with PSES enhancer. Cancer Res 65:1941–1951

    Article  PubMed  CAS  Google Scholar 

  43. Peter I, Graf C, Dummer R, Schaffner W, Greber UF, Hemmi S (2003) A novel attenuated replication-competent adenovirus for melanoma therapy. Gene Ther 10:530–539

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  45. Hsieh CL, Yang L, Miao L et al (2002) A novel targeting modality to enhance adenoviral replication by vitamin D(3) in androgen-independent human prostate cancer cells and tumors. Cancer Res 62:3084–3092

    PubMed  CAS  Google Scholar 

  46. Brunori M, Malerba M, Kashiwazaki H, Iggo R (2001) Replicating Adenoviruses That Target Tumors with Constitutive Activation of the Wnt Signaling Pathway. J Virol 75:2857–2865

    Article  PubMed  CAS  Google Scholar 

  47. Fuerer C, Iggo R (2002) 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 9:270–281

    Article  PubMed  CAS  Google Scholar 

  48. Lee SJ, Zhang Y, Lee SD et al (2004) Targeting prostate cancer with conditionally replicative adenovirus using PSMA enhancer. Mol Ther 10:1051–1058

    Article  PubMed  CAS  Google Scholar 

  49. Fechner H, Wang X, Srour M et al (2003) A novel tetracycline-controlled transactivator–transrepressor system enables external control of oncolytic adenovirus replication. Gene Ther 10:1680–1690

    Article  PubMed  CAS  Google Scholar 

  50. Chia MC, Shi W, Li JH et al (2004) A conditionally replicating adenovirus for nasopharyngeal carcinoma gene therapy. Mol Ther 9:804–817

    Article  PubMed  CAS  Google Scholar 

  51. Li Y, Yu DC, Chen Y et al (2001) A hepatocellular carcinoma-specific adenovirus variant, CV890, eliminates distant human liver tumors in combination with doxorubicin. Cancer Res 61:6428–6436

    PubMed  CAS  Google Scholar 

  52. Li Y, Chen Y, Dilley J et al (2003) Carcinoembryonic antigen-producing cell-specific oncolytic adenovirus, OV798, for colorectal cancer therapy. Mol Cancer Ther 2:1003–1009

    PubMed  CAS  Google Scholar 

  53. Banerjee NS, Rivera AA, Wang M et al (2004) Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/promoter-driven E1A, E4, or both in submerged cells and organotypic cultures. Mol Cancer Ther 3:437–449

    PubMed  CAS  Google Scholar 

  54. Buvoli M, Langer SJ, Bialik S, Leinwand LA (2002) Potential limitations of transcription terminators used as transgene insulators in adenoviral vectors. Gene Ther 9:227–231

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Hurtado Pico A, Wang X, Sipo I et al (2005) Viral and nonviral factors causing nonspecific replication of tumor- and tissue-specific promoter-dependent oncolytic adenoviruses. Mol Ther 11:563–577

    Article  PubMed  CAS  Google Scholar 

  57. Hatfield L, Hearing P (1991) Redundant elements in the adenovirus type 5 inverted terminal repeat promote bidirectional transcription in vitro and are important for virus growth in vivo. Virology 184:265–276

    Article  PubMed  CAS  Google Scholar 

  58. Yamamoto M, Davydova J, Takayama K, Alemany R, Curiel DT (2003) Transcription initiation activity of adenovirus left-end sequence in adenovirus vectors with e1 deleted. J Virol. 77:1633–1637

    Article  PubMed  CAS  Google Scholar 

  59. Proudfoot NJ (1986) Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation. Nature 322:562–565

    Article  PubMed  CAS  Google Scholar 

  60. Martin-Duque P, Jezzard S, Kaftansis L, Vassaux G (2004) Direct comparison of the insulating properties of two genetic elements in an adenoviral vector containing two different expression cassettes. Hum Gene Ther 15:995–1002

    Article  PubMed  CAS  Google Scholar 

  61. Vassaux G, Hurst HC, Lemoine NR (1999) Insulation of a conditionally expressed transgene in an adenoviral vector. Gene Ther 6:1192–1197

    Article  PubMed  CAS  Google Scholar 

  62. Steinwaerder DS, Lieber A (2000) Insulation from viral transcriptional regulatory elements improves inducible transgene expression from adenovirus vectors in vitro and in vivo. Gene Ther 7:556–567

    Article  PubMed  CAS  Google Scholar 

  63. Hearing P, Shenk T (1983) The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Cell 33:695–703

    Article  PubMed  CAS  Google Scholar 

  64. Miralles VJ, Cortes P, Stone N, Reinberg D (1989) The adenovirus inverted terminal repeat functions as an enhancer in a cell-free system. J Biol Chem 264:10763–10772

    PubMed  CAS  Google Scholar 

  65. Sassone-Corsi P, Hen R, Borrelli E, Leff T, Chambon P (1983) Far upstream sequences are required for efficient transcription from the adenovirus-2 E1A transcription unit. Nucleic Acids Res 11:8735–8745

    Article  PubMed  CAS  Google Scholar 

  66. West AG, Gaszner M, Felsenfeld G (2002) Insulators: many functions, many mechanisms. Genes Dev 16:271–288

    Article  PubMed  CAS  Google Scholar 

  67. Burcin MM, Schiedner G, Kochanek S, Tsai SY, O’Malley BW (1999) Adenovirus-mediated regulable target gene expression in vivo. Proc Natl Acad Sci USA 96:355–360

    Article  PubMed  CAS  Google Scholar 

  68. Majem M, Cascallo M, Bayo-Puxan N, Mesia R, Germa JR, Alemany R (2006) Control of E1A under an E2F-1 promoter insulated with the myotonic dystrophy locus insulator reduces the toxicity of oncolytic adenovirus Ad-Delta24RGD. Cancer Gene Ther 24:24

    Google Scholar 

  69. Jakubczak JL, Ryan P, Gorziglia M et al (2003) An oncolytic adenovirus selective for retinoblastoma tumor suppressor protein pathway-defective tumors: dependence on E1A, the E2F-1 promoter, and viral replication for selectivity and efficacy. Cancer Res 63:1490–1499

    PubMed  CAS  Google Scholar 

  70. Ko D, Hawkins L, Yu DC (2005) Development of transcriptionally regulated oncolytic adenoviruses. Oncogene 24:7763–7774

    Article  PubMed  CAS  Google Scholar 

  71. Sauthoff H, Pipiya T, Heitner S et al (2002) Late expression of p53 from a replicating adenovirus improves tumor cell killing and is more tumor cell specific than expression of the adenoviral death protein. Hum Gene Ther 13:1859–1871

    Article  PubMed  CAS  Google Scholar 

  72. Sova P, Ren XW, Ni S et al (2004) A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases. Mol Ther 9:496–509

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  75. Sarkar D, Su ZZ, Vozhilla N, Park ES, Gupta P, Fisher PB (2005) Dual cancer-specific targeting strategy cures primary and distant breast carcinomas in nude mice. Proc Natl Acad Sci USA 102:14034–14039 Epub 12005 Sep 14019

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  77. Hawkins LK, Johnson L, Bauzon M et al (2001) Gene delivery from the E3 region of replicating human adenovirus: evaluation of the 6.7 K/gp19 K region. Gene Ther 8:1123–1131

    Article  PubMed  CAS  Google Scholar 

  78. Rivera AA, Wang M, Suzuki K et al (2004) Mode of transgene expression after fusion to early or late viral genes of a conditionally replicating adenovirus via an optimized internal ribosome entry site in vitro and in vivo. Virology 320:121–134

    Article  PubMed  CAS  Google Scholar 

  79. Fuerer C, Iggo R (2004) 5-Fluorocytosine increases the toxicity of Wnt-targeting replicating adenoviruses that express cytosine deaminase as a late gene. Gene Ther 11:142–151

    Article  PubMed  CAS  Google Scholar 

  80. Jin F, Kretschmer PJ, Hermiston TW (2005) Identification of novel insertion sites in the Ad5 genome that utilize the Ad splicing machinery for therapeutic gene expression. Mol Ther 12:1052–1063 Epub 2005 Sep 1013

    Article  PubMed  CAS  Google Scholar 

  81. Lukashev AN, Fuerer C, Chen MJ, Searle P, Iggo R (2005) Late expression of nitroreductase in an oncolytic adenovirus sensitizes colon cancer cells to the prodrug CB1954. Hum Gene Ther 16:1473–1483

    Article  PubMed  CAS  Google Scholar 

  82. Akbulut H, Zhang L, Tang Y, Deisseroth A (2003) Cytotoxic effect of replication-competent adenoviral vectors carrying l-plastin promoter regulated E1A and cytosine deaminase genes in cancers of the breast, ovary and colon. Cancer Gene Ther 10:388–395

    Article  PubMed  CAS  Google Scholar 

  83. Davis JJ, Wang L, Dong F et al (2006) Oncolysis and suppression of tumor growth by a GFP-expressing oncolytic adenovirus controlled by an hTERT and CMV hybrid promoter. Cancer Gene Ther 17:17

    Google Scholar 

  84. Ono HA, Le LP, Davydova JG, Gavrikova T, Yamamoto M (2005) Noninvasive visualization of adenovirus replication with a fluorescent reporter in the E3 region. Cancer Res 65:10154–10158

    Article  PubMed  CAS  Google Scholar 

  85. Fujiwara T, Kagawa S, Kishimoto H et al (2006) Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent OBP-401 with docetaxel: preclinical evaluation of chemovirotherapy. Int J Cancer 119:432–440

    Article  PubMed  CAS  Google Scholar 

  86. Rajecki M, Kanerva A, Stenman UH et al (2007) Treatment of prostate cancer with Ad5/3Delta24hCG allows non-invasive detection of the magnitude and persistence of virus replication in vivo. Mol Cancer Ther 6:742–751

    Article  PubMed  CAS  Google Scholar 

  87. Ahmed A, Thompson J, Emiliusen L et al (2003) A conditionally replicating adenovirus targeted to tumor cells through activated RAS/P-MAPK-selective mRNA stabilization. Nat Biotechnol 21:771–777

    Article  PubMed  CAS  Google Scholar 

  88. Stoff-Khalili MA, Rivera AA, Nedeljkovic-Kurepa A et al (2007) Cancer-specific targeting of a conditionally replicative adenovirus using mRNA translational control. Breast Cancer Res Treat (in press) DOI 10.1007/s10549-007-9587-7

  89. Sipo I, Wang X, Hurtado Pico A et al (2006) Tamoxifen-regulated adenoviral E1A chimeras for the control of tumor selective oncolytic adenovirus replication in vitro and in vivo. Gene Ther 13:173–186

    Article  PubMed  CAS  Google Scholar 

  90. Liu Y, Ye T, Sun D, Maynard J, Deisseroth A (2004) Conditionally replication-competent adenoviral vectors with enhanced infectivity for use in gene therapy of melanoma. Hum Gene Ther 15:637–647

    Article  PubMed  CAS  Google Scholar 

  91. Davydova J, Le LP, Gavrikova T, Wang M, Krasnykh V, Yamamoto M (2004) Infectivity-enhanced cyclooxygenase-2-based conditionally replicative adenoviruses for esophageal adenocarcinoma treatment. Cancer Res 64:4319–4327

    Article  PubMed  CAS  Google Scholar 

  92. Rivera AA, Davydova J, Schierer S et al (2004) Combining high selectivity of replication with fiber chimerism for effective adenoviral oncolysis of CAR-negative melanoma cells. Gene Ther 11:1694–1702

    Article  PubMed  CAS  Google Scholar 

  93. Glasgow JN, Everts M, Curiel DT (2006) Transductional targeting of adenovirus vectors for gene therapy. Cancer Gene Ther 13:830–844

    Article  PubMed  CAS  Google Scholar 

  94. Waehler R, Russell SJ, Curiel DT (2007) Engineering targeted viral vectors for gene therapy. Nat Rev Genet 8:573–587

    Article  PubMed  CAS  Google Scholar 

  95. Reid T, Warren R, Kirn D (2002) Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther 9:979–986

    Article  PubMed  CAS  Google Scholar 

  96. Galanis E, Okuno SH, Nascimento AG et al (2005) Phase I-II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas. Gene Ther 12:437–445

    Article  PubMed  CAS  Google Scholar 

  97. Witlox MA, Lamfers ML, Wuisman PI, Curiel DT, Siegal GP (2007) Evolving gene therapy approaches for osteosarcoma using viral vectors: review. Bone 40:797–812

    Article  PubMed  CAS  Google Scholar 

  98. Jiang H, McCormick F, Lang FF, Gomez-Manzano C, Fueyo J (2006) Oncolytic adenoviruses as antiglioma agents. Expert Rev Anticancer Ther 6:697–708

    Article  PubMed  CAS  Google Scholar 

  99. Malerba M, Daeffler L, Rommelaere J, Iggo RD (2003) Replicating parvoviruses that target colon cancer cells. J Virol 77:6683–6691

    Article  PubMed  CAS  Google Scholar 

  100. Nakamura H, Kasuya H, Mullen JT et al (2002) Regulation of herpes simplex virus gamma(1)34.5 expression and oncolysis of diffuse liver metastases by Myb34.5. J Clin Invest 109:871–882

    PubMed  CAS  Google Scholar 

  101. Savontaus MJ, Sauter BV, Huang TG, Woo SL (2002) Transcriptional targeting of conditionally replicating adenovirus to dividing endothelial cells. Gene Ther 9:972–979

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The author apologizes to colleagues whose work could only be cited indirectly owing to space restrictions. Frequently, only individual examples for a specific strategy or virus could be cited for this reason. I thank Theron Johnson and Dominik Dorer (both Heidelberg) for their comments on the manuscript. Research in the author’s laboratory is supported by the Helmholtz Association of German Research Centres (HGF), the Deutsche Forschungsgemeinschaft (DFG), the Deutsche Krebshilfe e.V., the German Israeli Foundation, the Wilhelm Sander-Stiftung, and the Monika Kutzner-Stiftung.

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  1. Helmholtz-University Group Oncolytic Adenoviruses, German Cancer Research Center (DKFZ) and Heidelberg University Hospital, Heidelberg, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany

    Dirk M. Nettelbeck

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Nettelbeck, D.M. Cellular genetic tools to control oncolytic adenoviruses for virotherapy of cancer. J Mol Med 86, 363–377 (2008). https://doi.org/10.1007/s00109-007-0291-1

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