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Conditionally Replicating Adenoviruses for Cancer Treatment

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Cancer Gene Therapy

Part of the book series: Contemporary Cancer Research ((CCR))

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Abstract

Adenovirus is characterized by an icosahedral protein capsid 80 nm in diameter; it packages a 36-kb linear double-stranded deoxyribonucleic acid (DNA). A fiber protein projects from the 12 vertices of the capsid to interact with the cellular receptor. Among the more than 50 different types of human adenoviruses, type 5 has been mainly used to study the molecular biology of adenoviruses. This virus infects mainly epithelial cells (origin of most tumors) and causes a mild pathology with flulike symptoms. On infection, the DNA reaches the nucleus and is efficiently transcribed without insertion in the host genome.

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References

  1. Yoshida, K., Higashino, F., and Fujinaga, K. (1995) Transcriptional regulation of the adenovirus E1A gene. Curr. Top. Microbiol. Immunol. 199, 113–130.

    PubMed  CAS  Google Scholar 

  2. Hatfield, L. and 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 

  3. Osborne, T. F., Arvidson, D. N., Tyau, E. S., Dunsworth-Browne, M., and Berk, A. J. (1984) Transcription control region within the protein-coding portion of adenovirus E1A genes. Mol. Cell Biol. 4, 1293–1305.

    PubMed  CAS  Google Scholar 

  4. Hitt, M. M. and Graham, F. L. (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 

  5. Hallenbeck, P. L., Chang, Y. N., 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 

  6. Kurihara, T., Brough, D. E., Kovesdi, I., and Kufe, D. W. (2000) Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen. J. Clin. Invest. 106, 763–771.

    PubMed  CAS  Google Scholar 

  7. Tsukuda, K., Wiewrodt, R., Molnar-Kimber, K., Jovanovic, V. P., and Amin, K. M. (2002) An E2F-responsive replication-selective adenovirus targeted to the defective cell cycle in cancer cells: potent antitumoral efficacy but no toxicity to normal cell. Cancer Res. 62, 3438–3447.

    PubMed  CAS  Google Scholar 

  8. Black, A. R. and Azizkhan-Clifford, J. (1999) Regulation of E2F: a family of transcription factors involved in proliferation control. Gene 237, 281–302.

    Article  PubMed  CAS  Google Scholar 

  9. Adachi, Y., Reynolds, P. N., Yamamoto, M., et al. (2001) A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. Cancer Res. 61, 7882–7888.

    PubMed  CAS  Google Scholar 

  10. Ramachandra, M., Rahman, A., Zou, A., et al. (2001) Re-engineering adenovirus regulatory pathways to enhance oncolytic specificity and efficacy. Nat. Biotechnol. 19, 1035–1041.

    Article  PubMed  CAS  Google Scholar 

  11. Hernandez-Alcoceba, R., Pihalja, M., Wicha, M. S., and Clarke, M. F. (2000) A novel, conditionally replicative adenovirus for the treatment of breast cancer that allows controlled replication of E1a-deleted adenoviral vectors. Hum. Gene Ther. 11, 2009–2024.

    Article  PubMed  CAS  Google Scholar 

  12. Tauber, B. and Dobner, T. (2001) Molecular regulation and biological function of adenovirus early genes: the E4 ORFs. Gene 278, 1–23.

    Article  PubMed  CAS  Google Scholar 

  13. O’Connor, R. J. and Hearing, P. (2000) The E4-6/7 protein functionally compensates for the loss of E1A expression in adenovirus infection. J. Virol. 74, 5819–5824.

    Article  PubMed  CAS  Google Scholar 

  14. 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 

  15. Holm, P. S., Bergmann, S., Jurchott, K., et al. (2002) YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication by inducing E2 gene expression through the E2 late promoter. J. Biol. Chem. 277, 10,427–10,434.

    Article  PubMed  CAS  Google Scholar 

  16. Brunori, M., Malerba, M., Kashiwazaki, H., and 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 

  17. Carlson, C. A., Steinwaerder, D. S., Stecher, H., Shayakhmetov, D. M., and Lieber, A. (2002) Rearrangements in adenoviral genomes mediated by inverted repeats. Methods Enzymol. 346, 277–292.

    PubMed  CAS  Google Scholar 

  18. Yu, D. C., Chen, Y., Seng, M., Dilley, J., and Henderson, D. R. (1999) The addition of adenovirus type 5 region E3 enables calydon virus 787 to eliminate distant prostate tumor xenografts. Cancer Res. 59, 4200–4203; published erratum appears in Cancer Res. 2000, 60, 1150.

    PubMed  CAS  Google Scholar 

  19. 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 

  20. Yu, D. C., Sakamoto, G. T., and Henderson, D. R. (1999) Identification of the transcriptional regulatory sequences of human kallikrein 2 and their use in the construction of calydon virus 764, an attenuated replication competent adenovirus for prostate cancer therapy. Cancer Res. 59, 1498–1504.

    PubMed  CAS  Google Scholar 

  21. Vassaux, G., Hurst, H. C., and Lemoine, N. R. (1999) Insulation of a conditionally expressed transgene in an adenoviral vector. Gene Ther. 6, 1192–1197.

    Article  PubMed  CAS  Google Scholar 

  22. Buvoli, M., Langer, S. J., Bialik, S., and Leinwand, L. A. (2002) Potential limitations of transcription terminators used as transgene insulators in adenoviral vectors. Gene Ther. 9, 227–231.

    Article  PubMed  CAS  Google Scholar 

  23. Steinwaerder, D. S. and 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 

  24. Alemany, R., Lai, S., Lou, Y. C., Jan, H. Y., Fang, X., and Zhang, W. W. (1999) Complementary adenoviral vectors for oncolysis. Cancer Gene Ther. 6, 21–25.

    Article  PubMed  CAS  Google Scholar 

  25. Frisch, S. M. (1996) Reversal of malignancy by the adenovirus E1a gene. Mutat. Res. 350, 261–266.

    PubMed  Google Scholar 

  26. Frisch, S. M. and Mymryk, J. S. (2002) Adenovirus-5 E1A: paradox and paradigm. Nat. Rev. Mol. Cell Biol. 3, 441–452.

    Article  PubMed  CAS  Google Scholar 

  27. Bischoff, J. R., Kirn, D. H., 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 

  28. Fueyo, J., Gomez-Manzano, C., 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 

  29. 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 

  30. Howe, J. A., Demers, G. W., Johnson, D. E., et al. (2000) Evaluation of E1-mutant adenoviruses as conditionally replicating agents for cancer therapy. Mol. Ther. 2, 485–495.

    Article  PubMed  CAS  Google Scholar 

  31. Doronin, K., Toth, K., Kuppuswamy, M., Ward, P., Tollefson, A. E., and Wold, W. S. (2000) Tumor-specific, replication-competent adenovirus vectors overexpressing the adenovirus death protein. J. Virol. 74, 6147–6155.

    Article  PubMed  CAS  Google Scholar 

  32. Moran, E. (1994) Mammalian cell growth controls reflected through protein interactions with the adenovirus E1A gene products. Semin. Virol. 5, 327–340.

    Article  CAS  Google Scholar 

  33. Balague, C., Noya, F., Alemany, R., Chow, L. T., and Curiel, D. T. (2001) Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes. J. Virol. 75, 7602–7611.

    Article  PubMed  CAS  Google Scholar 

  34. Shen, Y., Kitzes, G., Nye, J. A., Fattaey, A., and Hermiston, T. (2001) Analyses of single-amino-acid substitution mutants of adenovirus type 5 E1B-55K protein. J. Virol. 75, 4297–4307.

    Article  PubMed  CAS  Google Scholar 

  35. Cuconati, A., Degenhardt, K., Sundararajan, R., Anschel, A., and White, E. (2002) Bak and Bax function to limit adenovirus replication through apoptosis induction. J. Virol. 76, 4547–4558.

    Article  PubMed  CAS  Google Scholar 

  36. Nevels, M., Spruss, T., Wolf, H., and Dobner, T. (1999) The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53. Oncogene 18, 9–17.

    Article  PubMed  CAS  Google Scholar 

  37. Mundschau, L. J. and Faller, D. V. (1992) Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic initiation factor 2 alpha-kinase activation. J. Biol. Chem. 267, 23,092–23,098.

    PubMed  CAS  Google Scholar 

  38. Thimmappaya, B., Weinberger, C., Schneider, R. J., and Shenk, T. (1982) Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell 31, 543–551.

    Article  PubMed  CAS  Google Scholar 

  39. Strong, J. E., Coffey, M. C., Tang, D., Sabinin, P., and Lee, P. W. (1998) The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J. 17, 3351–3362.

    Article  PubMed  CAS  Google Scholar 

  40. Bergmann, M., Romirer, I., Sachet, M., et al. (2001) A genetically engineered influenza A virus with ras-dependent oncolytic properties. Cancer Res. 61, 8188–8193.

    PubMed  CAS  Google Scholar 

  41. Bolovan, C. A., Sawtell, N. M., and Thompson, R. L. (1994) ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for neurovirulence in mice and for replication in confluent primary mouse embryo cell cultures. J. Virol. 68, 48–55.

    PubMed  CAS  Google Scholar 

  42. Stojdl, D. F., Lichty, B., Knowles, S., et al. (2000) Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat. Med. 6, 821–825.

    Article  PubMed  CAS  Google Scholar 

  43. Nettelbeck, D. M., Rivera, A. A., Balague, C., Alemany, R., and Curiel, D. T. (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 

  44. 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 

  45. Sauthoff, H., Heitner, S., Rom, W. N., and Hay, J. G. (2000) Deletion of the adenoviral E1b-19kD gene enhances tumor cell killing of a replicating adenoviral vector. Hum. Gene Ther. 11, 379–388.

    Article  PubMed  CAS  Google Scholar 

  46. Chiou, S. K. and White, E. (1998) Inhibition of ICE-like proteases inhibits apoptosis and increases virus production during adenovirus infection. Virology 244, 108–118.

    Article  PubMed  CAS  Google Scholar 

  47. White, E., Faha, B., and Stillman, B. (1986) Regulation of adenovirus gene expression in human WI38 cells by an E1B-encoded tumor antigen. Mol. Cell Biol. 6, 3763–3773.

    PubMed  CAS  Google Scholar 

  48. Wildner, O., Blaese, R. M., and Morris, J. C. (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 

  49. Rogulski, K. R., Wing, M. S., Paielli, D. L., Gilbert, J. D., Kim, J. H., and Freytag, S. O. (2000) 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.

    Article  PubMed  CAS  Google Scholar 

  50. Freytag, S. O., Rogulski, K. R., Paielli, D. L., Gilbert, J. D., and Kim, J. H. (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 

  51. Li, H., Haviv, Y. S., Derdeyn, C. A., et al. (2001) 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. 12, 2155–2165.

    Article  PubMed  CAS  Google Scholar 

  52. Suzuki, K., Fueyo, J., Krasnykh, V., Reynolds, P. N., Curiel, D. T., and Alemany, R. (2001) A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin. Cancer Res. 7, 120–126.

    PubMed  CAS  Google Scholar 

  53. Hemminki, A., Dmitriev, I., Liu, B., Desmond, R. A., Alemany, R., and Curiel, D. T. (2001) Targeting oncolytic adenoviral agents to the epidermal growth factor pathway with a secretory fusion molecule. Cancer Res. 61, 6377–6381.

    PubMed  CAS  Google Scholar 

  54. Heise, C., Lemmon, M., and Kirn, D. (2000) 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. 6, 4908–4914.

    PubMed  CAS  Google Scholar 

  55. Khuri, F. R., Nemunaitis, J., Ganly, I., et al. (2000) 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. 6, 879–885.

    Article  PubMed  CAS  Google Scholar 

  56. Bernt, K. M., Steinwaerder, D. S., Ni, S., Li, Z. Y., Roffler, S. R., and Lieber, A. (2002) Enzyme-activated prodrug therapy enhances tumor-specific replication of adenovirus vectors. Cancer Res. 62, 6089–6098.

    PubMed  CAS  Google Scholar 

  57. Seidman, M. A., Hogan, S. M., Wendland, R. L., Worgall, S., Crystal, R. G., and Leopold, P. L. (2001) Variation in adenovirus receptor expression and adenovirus vector-mediated transgene expression at defined stages of the cell cycle. Mol. Ther. 4, 13–21.

    Article  PubMed  CAS  Google Scholar 

  58. Steinwaerder, D. S., Carlson, C. A., and Lieber, A. (2000) DNA replication of first-generation adenovirus vectors in tumor cells. Hum. Gene Ther. 11, 1933–1948.

    Article  PubMed  CAS  Google Scholar 

  59. Li, Y., Yu, D. C., 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 

  60. Yu, D. C., Chen, Y., Dilley, J., et al. (2001) Antitumor synergy of CV787, a prostate cancer-specific adenovirus, and paclitaxel and docetaxel. Cancer Res. 61, 517–525.

    PubMed  CAS  Google Scholar 

  61. Rogulski, K. R., Freytag, S. O., Zhang, K., et al. (2000) In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy. Cancer Res. 60, 1193–1196.

    PubMed  CAS  Google Scholar 

  62. Chen, Y., Yu, D. C., Charlton, D., and Henderson, D. R. (2000) Pre-existent adenovirus antibody inhibits systemic toxicity and antitumor activity of CN706 in the nude mouse LNCaP xenograft model: implications and proposals for human therapy. Hum. Gene Ther. 11, 1553–1567.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Gene Therapy Program, Institut Catalá d’Oncologia, Barcelona, Spain

    Ramon Alemany

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  1. Ramon Alemany
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Editors and Affiliations

  1. Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL

    David T. Curiel MD, PhD  & Joanne T. Douglas PhD  & 

  2. Division of Human Gene Therapy, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL

    David T. Curiel MD, PhD  & Joanne T. Douglas PhD  & 

  3. Division of Human Gene Therapy, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL

    David T. Curiel MD, PhD  & Joanne T. Douglas PhD  & 

  4. Division of Human Gene Therapy, Department of Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL

    David T. Curiel MD, PhD  & Joanne T. Douglas PhD  & 

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© 2005 Humana Press Inc., Totowa, NJ

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Alemany, R. (2005). Conditionally Replicating Adenoviruses for Cancer Treatment. In: Curiel, D.T., Douglas, J.T. (eds) Cancer Gene Therapy. Contemporary Cancer Research. Humana Press. https://doi.org/10.1007/978-1-59259-785-7_15

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