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:

Herpes simplex virus 1 (HSV-1) for cancer treatment

Cancer Gene Therapy volume 13, pages 975–992 (2006)Cite this article

Abstract

Cancer remains a serious threat to human health, causing over 500 000 deaths each year in US alone, exceeded only by heart diseases. Many new technologies are being developed to fight cancer, among which are gene therapies and oncolytic virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus with many favorable properties both as a delivery vector for cancer therapeutic genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if harnessed and made to be selective by genetic manipulations, makes this virus a good candidate for developing viral oncolytic approach. Furthermore, its large genome size, ability to infect cells with a high degree of efficiency, and the presence of an inherent replication controlling mechanism, the thymidine kinase gene, add to its potential capabilities. This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment.

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. Lerner AM . Infections with herpes simplex virus. In: Adams RD, Braunwald E, Petersdorf RG, Wilson JD (eds). Harrison's Principles of Internal Medicine. McGraw-Hill, Inc.: New York, 1980, pp 847–852.

    Google Scholar 

  2. Zhou ZH, Chen DH, Jakana J, Rixon FJ, Chui W . Visualization of tegument–capsid interactions and DNA in intact herpes simplex virus type 1 virions. J Virol 1999; 73: 3210–3218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Herold BC, WuDunn D, Soltys N, Spear PG . Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity. J Virol 1991; 65: 1090–1098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Herold BC, Visalli RJ, Susmarskin N, Brandt CR, Spear PG . Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. J Gen Virol 1994; 75 (Part 6): 1211–1222.

    Article  CAS  PubMed  Google Scholar 

  5. Spear PG, Shieh MT, Herold BC, Wudunn D, Koshy TI . Heparan sulfate glycosaminoglycans as primary cell surface receptors for herpes simplex virus. Adv Exp Med Biol 1992; 313: 341–353.

    Article  CAS  PubMed  Google Scholar 

  6. Spear PG . Herpes simplex virus: receptors and ligands for cell entry. Cell Microbiol 2004; 6: 401–410.

    Article  CAS  PubMed  Google Scholar 

  7. Cai WH, Gu B, Person S . Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion. J Virol 1988; 62: 2596–2604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fuller AO, Santos RE, Spear PG . Neutralizing antibodies specific for glycoprotein H of herpes simplex virus permit viral attachment to cells but prevent penetration. J Virol 1989; 63: 3435–3443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Roop C, Hutchinson L, Johnson DC . A mutant herpes simplex virus type 1 unable to express glycoprotein L cannot enter cells, and its particles lack glycoprotein H. J Virol 1993; 67: 2285–2297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. DeLuca N, Bzik D, Person S, Snipes W . Early events in herpes simplex virus type 1 infection: photosensitivity of fluorescein isothiocyanate-treated virions. Proc Natl Acad Sci USA 1981; 78: 912–916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sodeik B, Ebersold MW, Helenius A . Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus. J Cell Biol 1997; 136: 1007–1021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Roizman B, Knipe DM . Herpes Simplex Viruses and their Replication. Lippincott Williams & Wilkins: Phladelphia, 2001.

    Google Scholar 

  13. Burton EA, Fink DJ, Glorioso JC . Gene delivery using herpes simplex virus vectors. DNA Cell Biol 2002; 21: 915–936.

    Article  CAS  PubMed  Google Scholar 

  14. Mocarski ES, Roizman B . Structure and role of the herpes simplex virus DNA termini in inversion, circularization and generation of virion DNA. Cell 1982; 31: 89–97.

    Article  CAS  PubMed  Google Scholar 

  15. Jacob RJ, Morse LS, Roizman B . Anatomy of herpes simplex virus DNA. XII. Accumulation of head-to-tail concatemers in nuclei of infected cells and their role in the generation of the four isomeric arrangements of viral DNA. J Virol 1979; 29: 448–457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Steven AC, Spear PG . Herpesvirus Capsid Assembly and Envelopment. Oxford University Press: New York, 1997.

    Google Scholar 

  17. Homa FL, Brown JC . Capsid assembly and DNA packaging in herpes simplex virus. Rev Med Virol 1997; 7: 107–122.

    Article  CAS  PubMed  Google Scholar 

  18. Rixon FJ, Addison C, McGregor A, Macnab SJ, Nicholson P, Preston VG et al. Multiple interactions control the intracellular localization of the herpes simplex virus type 1 capsid proteins. J Gen Virol 1996; 77 (Part 9): 2251–2260.

    Article  CAS  PubMed  Google Scholar 

  19. Boehmer PE, Lehman IR . Herpes simplex virus DNA replication. Annu Rev Biochem 1997; 66: 347–384.

    Article  CAS  PubMed  Google Scholar 

  20. Deiss LP, Chou J, Frenkel N . Functional domains within the a sequence involved in the cleavage-packaging of herpes simplex virus DNA. J Virol 1986; 59: 605–618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Taylor TJ, Brockman MA, McNamee EE, Knipe DM . Herpes simplex virus. Front Biosci 2002; 7: d752–d764.

    Article  CAS  PubMed  Google Scholar 

  22. Efstathiou S, Minson AC, Field HJ, Anderson JR, Wildy P . Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans. J Virol 1986; 57: 446–455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wagner EK, Bloom DC . Experimental investigation of herpes simplex virus latency. Clin Microbiol Rev 1997; 10: 419–443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Croen KD, Ostrove JM, Dragovic LJ, Smialek JE, Straus SE . Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene ‘anti-sense’ transcript by in situ hybridization. N Engl J Med 1987; 317: 1427–1432.

    Article  CAS  PubMed  Google Scholar 

  25. Rock DL, Nesburn AB, Ghiasi H, Ong J, Lewis TL, Lokensgard JR et al. Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. J Virol 1987; 61: 3820–3826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Spivack JG, Fraser NW . Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J Virol 1987; 61: 3841–3847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT . RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 1987; 235: 1056–1059.

    Article  CAS  PubMed  Google Scholar 

  28. Javier RT, Stevens JG, Dissette VB, Wagner EK . A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state. Virology 1988; 166: 254–257.

    Article  CAS  PubMed  Google Scholar 

  29. Sedarati F, Izumi KM, Wagner EK, Stevens JG . Herpes simplex virus type 1 latency-associated transcription plays no role in establishment or maintenance of a latent infection in murine sensory neurons. J Virol 1989; 63: 4455–4458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ho DY, Mocarski ES . Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proc Natl Acad Sci USA 1989; 86: 7596–7600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Steiner I, Spivack JG, Lirette RP, Brown SM, MacLean AR, Subak-Sharpe JH et al. Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO J 1989; 8: 505–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kent JR, Kang W, Miller CG, Fraser NW . Herpes simplex virus latency-associated transcript gene function. J Neurovirol 2003; 9: 285–290.

    Article  CAS  PubMed  Google Scholar 

  33. Bloom DC . HSV LAT and neuronal survival. Int Rev Immunol 2004; 23: 187–198.

    Article  CAS  PubMed  Google Scholar 

  34. Miller CS, Danaher RJ, Jacob RJ . Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence. Crit Rev Oral Biol Med 1998; 9: 541–562.

    Article  CAS  PubMed  Google Scholar 

  35. Goodkin ML, Morton ER, Blaho JA . Herpes simplex virus infection and apoptosis. Int Rev Immunol 2004; 23: 141–172.

    Article  CAS  PubMed  Google Scholar 

  36. Hill A, Jugovic P, York I, Russ G, Bennink J, Yewdell J et al. Herpes simplex virus turns off the TAP to evade host immunity. Nature 1995; 375: 411–415.

    Article  CAS  PubMed  Google Scholar 

  37. Fruh K, Ahn K, Djaballah H, Sempe P, van Endert PM, Tampe R et al. A viral inhibitor of peptide transporters for antigen presentation. Nature 1995; 375: 415–418.

    Article  CAS  PubMed  Google Scholar 

  38. Matis J, Kudelova M . Early shutoff of host protein synthesis in cells infected with herpes simplex viruses. Acta Virol 2001; 45: 269–277.

    CAS  PubMed  Google Scholar 

  39. Everett RD, Earnshaw WC, Findlay J, Lomonte P . Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. EMBO J 1999; 18: 1526–1538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Advani SJ, Brandimarti R, Weichselbaum RR, Roizman B . The disappearance of cyclins A and B and the increase in activity of the G(2)/M-phase cellular kinase cdc2 in herpes simplex virus 1-infected cells require expression of the alpha22/U(S)1.5 and U(L)13 viral genes. J Virol 2000; 74: 8–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Spencer CA, Dahmus ME, Rice SA . Repression of host RNA polymerase II transcription by herpes simplex virus type 1. J Virol 1997; 71: 2031–2040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sandri-Goldin RM . Properties of an HSV-1 regulatory protein that appears to impair host cell splicing. Infect Agents Dis 1994; 3: 59–67.

    CAS  PubMed  Google Scholar 

  43. 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 

  44. Chou J, Roizman B . The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. Proc Natl Acad Sci USA 1992; 89: 3266–3270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. He B, Gross M, Roizman B . The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci USA 1997; 94: 843–848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Valyi-Nagy T, Fareed MU, O'Keefe JS, Gesser RM, MacLean AR, Brown SM et al. The herpes simplex virus type 1 strain 17+ gamma 34.5 deletion mutant 1716 is avirulent in SCID mice. J Gen Virol 1994; 75 (Part 8): 2059–2063.

    Article  CAS  PubMed  Google Scholar 

  47. Bolovan CA, Sawtell NM, Thompson RL . 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 1994; 68: 48–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wakimoto H, Johnson PR, Knipe DM, Chiocca EA . Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells. Gene Therapy 2003; 10: 983–990.

    Article  CAS  PubMed  Google Scholar 

  49. Wakimoto H, Fulci G, Tyminski E, Chiocca EA . Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide's enhancement of viral oncolysis. Gene Therapy 2004; 11: 214–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ikeda K, Ichikawa T, Wakimoto H, Silver JS, Deisboeck TS, Finkelstein D et al. Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nat Med 1999; 5: 881–887.

    Article  CAS  PubMed  Google Scholar 

  51. Morahan PS, Thomson TA, Kohl S, Murray BK . Immune responses to labial infection of BALB/c mice with herpes simplex virus type 1. Infect Immun 1981; 32: 180–187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kapoor AK, Nash AA, Wildy P . Pathogenesis of herpes simplex virus in B cell-suppressed mice: the relative roles of cell-mediated and humoral immunity. J Gen Virol 1982; 61 (Part l): 127–131.

    Article  PubMed  Google Scholar 

  53. Kapoor AK, Nash AA, Wildy P, Phelan J, McLean CS, Field HJ . Pathogenesis of herpes simplex virus in congenitally athymic mice: the relative roles of cell-mediated and humoral immunity. J Gen Virol 1982; 60: 225–233.

    Article  CAS  PubMed  Google Scholar 

  54. Lopez C . Genetics of natural resistance to herpesvirus infections in mice. Nature 1975; 258: 152–153.

    Article  CAS  PubMed  Google Scholar 

  55. Lopez C . Resistance to HSV-1 in the mouse is governed by two major, independently segregating, non-H-2 loci. Immunogenetics 1980; 11: 87–92.

    Article  CAS  PubMed  Google Scholar 

  56. Koelle DM, Corey L . Recent progress in herpes simplex virus immunobiology and vaccine research. Clin Microbiol Rev 2003; 16: 96–113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kobelt D, Lechmann M, Steinkasserer A . The interaction between dendritic cells and herpes simplex virus-1. Curr Top Microbiol Immunol 2003; 276: 145–161.

    CAS  PubMed  Google Scholar 

  58. Pollara G, Katz DR, Chain BM . The host response to herpes simplex virus infection. Curr Opin Infect Dis 2004; 17: 199–203.

    Article  CAS  PubMed  Google Scholar 

  59. Bowers WJ, Olschowka JA, Federoff HJ . Immune responses to replication-defective HSV-1 type vectors within the CNS: implications for gene therapy. Gene Therapy 2003; 10: 941–945.

    Article  CAS  PubMed  Google Scholar 

  60. Stanberry LR . Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines. Herpes 2004; 11 (Suppl 3): 161A–169A.

    PubMed  Google Scholar 

  61. Nash AA, Jayasuriya A, Phelan J, Cobbold SP, Waldmann H, Prospero T . Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. J Gen Virol 1987; 68 (Part 3): 825–833.

    Article  PubMed  Google Scholar 

  62. Sethi KK, Omata Y, Schneweis KE . Protection of mice from fatal herpes simplex virus type 1 infection by adoptive transfer of cloned virus-specific and H-2-restricted cytotoxic T lymphocytes. J Gen Virol 1983; 64 (Part 2): 443–447.

    Article  PubMed  Google Scholar 

  63. Leung KN, Nash AA, Sia DY, Wildy P . Clonal analysis of T-cell responses to herpes simplex virus: isolation, characterization and antiviral properties of an antigen-specific helper T-cell clone. Immunology 1984; 53: 623–633.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Bonneau RH, Jennings SR . Modulation of acute and latent herpes simplex virus infection in C57BL/6 mice by adoptive transfer of immune lymphocytes with cytolytic activity. J Virol 1989; 63: 1480–1484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fraefel C, Jacoby DR, Breakefield XO . Herpes simplex virus type 1-based amplicon vector systems. Adv Virus Res 2000; 55: 425–451.

    Article  CAS  PubMed  Google Scholar 

  66. Link CJ, Hellrung DJ, Seregina T, Wang S . Eliciting hyperacute rejection as a tumor killing strategy. Herpes amplicon vector transfer of the alpha(1,3)galactosyltransferase gene. Adv Exp Med Biol 2000; 465: 217–227.

    Article  CAS  PubMed  Google Scholar 

  67. Federoff HJ, Halterman MW, Brooks AI . Use of the herpes amplicon system as a vehicle for somatic gene transfer. Adv Drug Deliv Rev 1997; 27: 29–39.

    Article  CAS  PubMed  Google Scholar 

  68. Frenkel N, Singer O, Kwong AD . Minireview: the herpes simplex virus amplicon – a versatile defective virus vector. Gene Therapy 1994; 1 (Suppl 1): S40–S46.

    PubMed  Google Scholar 

  69. Sacks WR, Greene CC, Aschman DP, Schaffer PA . Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol 1985; 55: 796–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. DeLuca NA, McCarthy AM, Schaffer PA . Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol 1985; 56: 558–570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Johnson PA, Miyanohara A, Levine F, Cahill T, Friedmann T . Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1. J Virol 1992; 66: 2952–2965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wu N, Watkins SC, Schaffer PA, DeLuca NA . Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22. J Virol 1996; 70: 6358–6369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Samaniego LA, Neiderhiser L, DeLuca NA . Persistence and expression of the herpes simplex virus genome in the absence of immediate-early proteins. J Virol 1998; 72: 3307–3320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Krisky DM, Wolfe D, Goins WF, Marconi PC, Ramakrishnan R, Mata M et al. Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Therapy 1998; 5: 1593–1603.

    Article  CAS  PubMed  Google Scholar 

  75. Ace CI, McKee TA, Ryan JM, Cameron JM, Preston CM . Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression. J Virol 1989; 63: 2260–2269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Preston CM, Mabbs R, Nicholl MJ . Construction and characterization of herpes simplex virus type 1 mutants with conditional defects in immediate early gene expression. Virology 1997; 229: 228–239.

    Article  CAS  PubMed  Google Scholar 

  77. Preston CM, Nicholl MJ . Repression of gene expression upon infection of cells with herpes simplex virus type 1 mutants impaired for immediate-early protein synthesis. J Virol 1997; 71: 7807–7813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Farrell HE, McLean CS, Harley C, Efstathiou S, Inglis S, Minson AC . Vaccine potential of a herpes simplex virus type 1 mutant with an essential glycoprotein deleted. J Virol 1994; 68: 927–932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Forrester A, Lipsey JR, Teitelbaum ML, DePaulo JR, Andrzejewski PL . Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. J Virol 1992; 66: 341–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gupta N . Current status of viral gene therapy for brain tumours. Expert Opin Invest Drugs 2000; 9: 713–726.

    Article  CAS  Google Scholar 

  81. al-Rikabi AC, al-Sohaibani MO, Jamjoom A, al-Rayess MM . Metastatic deposits of a high-grade malignant glioma in cervical lymph nodes diagnosed by fine needle aspiration (FNA) cytology – case report and literature review. Cytopathology 1997; 8: 421–427.

    Article  CAS  PubMed  Google Scholar 

  82. Hsu E, Keene D, Ventureyra E, Matzinger MA, Jimenez C, Wang HS et al. Bone marrow metastasis in astrocytic gliomata. J Neurooncol 1998; 37: 285–293.

    Article  CAS  PubMed  Google Scholar 

  83. Spencer DM . Developments in suicide genes for preclinical and clinical applications. Curr Opin Mol Ther 2000; 2: 433–440.

    CAS  PubMed  Google Scholar 

  84. Field HJ, Wildy P . The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (London) 1978; 81: 267–277.

    Article  CAS  Google Scholar 

  85. Chrisp CE, Sunstrum JC, Averill Jr DR, Levine M, Glorioso JC . Characterization of encephalitis in adult mice induced by intracerebral inoculation of herpes simplex virus type 1 (KOS) and comparison with mutants showing decreased virulence. Lab Invest 1989; 60: 822–830.

    CAS  PubMed  Google Scholar 

  86. Efstathiou S, Kemp S, Darby G, Minson AC . The role of herpes simplex virus type 1 thymidine kinase in pathogenesis. J Gen Virol 1989; 70 (Part 4): 869–879.

    Article  CAS  PubMed  Google Scholar 

  87. Moriuchi S, Oligino T, Krisky d, Marconi P, Fink D, Cohen J et al. Enhanced tumor cell killing in the presence of ganciclovir by herpes simplex virus type 1 vector-directed coexpression of human tumor necrosis factor-alpha and herpes simplex virus thymidine kinase. Cancer Res 1998; 58: 5731–5737.

    CAS  PubMed  Google Scholar 

  88. Miyatake S, Martuza RL, Rabkin SD . Defective herpes simplex virus vectors expressing thymidine kinase for the treatment of malignant glioma. Cancer Gene Ther 1997; 4: 222–228.

    CAS  PubMed  Google Scholar 

  89. Maria BL, Friedman T . Gene therapy for pediatric brain tumors. Semin Pediatr Neurol 1997; 4: 333–339.

    Article  CAS  PubMed  Google Scholar 

  90. Freeman SM, Whartenby KA, Freeman JL, Abboud CN, Marrogi AJ . In situ use of suicide genes for cancer therapy. Semin Oncol 1996; 23: 31–45.

    CAS  PubMed  Google Scholar 

  91. van Dillen IJ, Mulder NH, Vaalburg W, de Vries EF, Hospers GA . Influence of the bystander effect on HSV-tk/GCV gene therapy. A review. Curr Gene Ther 2002; 2: 307–322.

    Article  CAS  PubMed  Google Scholar 

  92. Nicholas TW, Read SB, Burrows FJ, Kruse CA . Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects. Histol Histopathol 2003; 18: 495–507.

    CAS  PubMed  Google Scholar 

  93. Naus CC, Bechberger JF, Zhang Y, Venance L, Yamasaki H, Juneja SC et al. Altered gap junctional communication, intercellular signaling, and growth in cultured astrocytes deficient in connexin43. J Neurosci Res 1997; 49: 528–540.

    Article  CAS  PubMed  Google Scholar 

  94. Yamasaki H, Krutovskikh V, Mesnil M, Tanaka T, Zaidan-Dagli ML, Omori Y . Role of connexin (gap junction) genes in cell growth control and carcinogenesis. CR Acad Sci III 1999; 322: 151–159.

    Article  CAS  Google Scholar 

  95. Marconi P, Tamura M, Moriuchi S, Krisky DM, Niranjan A, Goins WF et al. Connexin 43-enhanced suicide gene therapy using herpesviral vectors. Mol Ther 2000; 1: 71–81.

    Article  CAS  PubMed  Google Scholar 

  96. Burton EA, Wechuck JB, Wendell SK, Goins WF, Fink DJ, Glorioso JC . Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells 2001; 19: 358–377.

    Article  CAS  PubMed  Google Scholar 

  97. Rosenfeld MR, Meneses P, Dalmau J, Drobnjak M, Cordon-Cardo C, Kaplitt MG . Gene transfer of wild-type p53 results in restoration of tumor-suppressor function in a medulloblastoma cell line. Neurology 1995; 45: 1533–1539.

    Article  CAS  PubMed  Google Scholar 

  98. Hoshi M, Harada A, Kawase T, Uyemura K, Yazaki T . Antitumoral effects of defective herpes simplex virus-mediated transfer of tissue inhibitor of metalloproteinases-2 gene in malignant glioma U87 in vitro: consequences for anti-cancer gene therapy. Cancer Gene Ther 2000; 7: 799–805.

    Article  CAS  PubMed  Google Scholar 

  99. Tung C, Federoff HJ, Brownlee M, Karpoff H, Weigel T, Brennan MF et al. Rapid production of interleukin-2-secreting tumor cells by herpes simplex virus-mediated gene transfer: implications for autologous vaccine production. Hum Gene Ther 1996; 7: 2217–2224.

    Article  CAS  PubMed  Google Scholar 

  100. Kim SH, Carew JF, Kooby DA, Shields J, Entwisle C, Patel S et al. Combination gene therapy using multiple immunomodulatory genes transferred by a defective infectious single-cycle herpes virus in squamous cell cancer. Cancer Gene Ther 2000; 7: 1279–1285.

    Article  CAS  PubMed  Google Scholar 

  101. Toda M, Martuza RL, Kojima H, Rabkin SD . In situ cancer vaccination: an IL-12 defective vector/replication-competent herpes simplex virus combination induces local and systemic antitumor activity. J Immunol 1998; 160: 4457–4464.

    CAS  PubMed  Google Scholar 

  102. Kanno H, Hattori S, Sato H, Murata H, Huang FH, Hayashi A et al. Experimental gene therapy against subcutaneously implanted glioma with a herpes simplex virus-defective vector expressing interferon-gamma. Cancer Gene Ther 1999; 6: 147–154.

    Article  CAS  PubMed  Google Scholar 

  103. Toda M, Martuza RL, Rabkin SD . Tumor growth inhibition by intratumoral inoculation of defective herpes simplex virus vectors expressing granulocyte–macrophage colony-stimulating factor. Mol Ther 2000; 2: 324–329.

    Article  CAS  PubMed  Google Scholar 

  104. Niranjan A, Moriuchi S, Lunsford LD, Kondziolka D, Flickinger JC, Fellows W et al. Effective treatment of experimental glioblastoma by HSV vector-mediated TNF alpha and HSV-tk gene transfer in combination with radiosurgery and ganciclovir administration. Mol Ther 2000; 2: 114–120.

    Article  CAS  PubMed  Google Scholar 

  105. Niranjan A, Wolfe D, Tamura M, Soares MK, Krisky DM, Lunsford LD et al. Treatment of rat gliosarcoma brain tumors by HSV-based multigene therapy combined with radiosurgery. Mol Ther 2003; 8: 530–542.

    Article  CAS  PubMed  Google Scholar 

  106. Toda M, Martuza RL, Rabkin SD . Combination suicide/cytokine gene therapy as adjuvants to a defective herpes simplex virus-based cancer vaccine. Gene Therapy 2001; 8: 332–339.

    Article  CAS  PubMed  Google Scholar 

  107. Moriuchi S, glorioso JC, Maruno M, Izumoto S, Wolfe D, Huang S et al. Combination gene therapy for glioblastoma involving herpes simplex virus vector-mediated codelivery of mutant IkappaBalpha and HSV thymidine kinase. Cancer Gene Ther 2005; 5: 487–496.

    Article  CAS  Google Scholar 

  108. Moriuchi S, Wolfe d, Tamura M, Yoshimine T, Miura F, Cohen JB et al. Double suicide gene therapy using a replication defective herpes simplex virus vector reveals reciprocal interference in a malignant glioma model. Gene Therapy 2002; 9: 584–591.

    Article  CAS  PubMed  Google Scholar 

  109. Dock G . Rabies virus vaccination in a patient with cervical carcinoma. Am J Med Sci 1904; 127: 563.

    Article  Google Scholar 

  110. Bischoff JR, Kim 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 

  111. 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 

  112. McCormick F . Cancer-specific viruses and the development of ONYX-015. Cancer Biol Ther 2003; 2: S157–S160.

    Article  CAS  PubMed  Google Scholar 

  113. Reid T, Galanis E, Abbruzzese J, Sze D, Wein LM, Andrews J et al. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints. Cancer Res 2002; 62: 6070–6079.

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  115. Kirn D . Oncolytic virotherapy as a novel treatment platform for cancer. Ernst Schering Research Foundation Workshop 2003 pp 89–105.

  116. Nemunaitis J . Live viruses in cancer treatment. Oncology (Huntingt) 2002; 16: 1483–1492; discussion 1495–1487.

    Google Scholar 

  117. Nemunaitis J, Edelman J . Selectively replicating viral vectors. Cancer Gene Ther 2002; 9: 987–1000.

    Article  CAS  PubMed  Google Scholar 

  118. Shenk TE . Adenoviridae: The Viruses and their Replication. Lippincott Williams & Wilkins: Philadelphia, 2001.

    Google Scholar 

  119. Dingwell KS, brunette CR, Hendricks RL, Tang O, Tang M, Rainbow AJ et al. Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. J Virol 1994; 68: 834–845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Dingwell KS, Johnson DC . The herpes simplex virus gE-gI complex facilitates cell-to-cell spread and binds to components of cell junctions. J Virol 1998; 72: 8933–8942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. De Clercq E, Andrei g, Snoeck R, De Bolle L, Naesens L, Degreve B et al. Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents. Nucleosides Nucleotides Nucleic Acids 2001; 20: 271–285.

    Article  CAS  PubMed  Google Scholar 

  122. De Clercq E . Antiviral drugs in current clinical use. J Clin Virol 2004; 30: 115–133.

    Article  CAS  PubMed  Google Scholar 

  123. Kirn D, Martuza RL, Zwiebel J . Replication-selective virotherapy for cancer: biological principles, risk management and future directions. Nat Med 2001; 7: 781–787.

    Article  CAS  PubMed  Google Scholar 

  124. Dobbelstein M . Replicating adenoviruses in cancer therapy. Curr Top Microbiol Immunol 2004; 273: 291–334.

    CAS  PubMed  Google Scholar 

  125. Lou E . Oncolytic herpes viruses as a potential mechanism for cancer therapy. Acta Oncol 2003; 42: 660–671.

    Article  PubMed  Google Scholar 

  126. DeWeese TL, van der Poel H, Li S, Mikhak B, Drew R, Goemann M et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res 2001; 61: 7464–7472.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  128. Curiel DT . Strategies to adapt adenoviral vectors for targeted delivery. Ann NY Acad Sci 1999; 886: 158–171.

    Article  CAS  PubMed  Google Scholar 

  129. Goins WF, Wolfe D, Krisky DM, Bai Q, Burton EA, Fink DJ et al. Delivery using herpes simplex virus: an overview. Methods Mol Biol 2004; 246: 257–299.

    CAS  PubMed  Google Scholar 

  130. Martuza RL, Malick A, Market 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 

  131. Markert JM, Coen DM, Malick A, Mineta T, Martuza RL . Expanded spectrum of viral therapy in the treatment of nervous system tumors. J Neurosurg 1992; 77: 590–594.

    Article  CAS  PubMed  Google Scholar 

  132. Jia WW, McDermott M, Goldie J, Cynader M, Tan J, Tufaro F . Selective destruction of gliomas in immunocompetent rats by thymidine kinase-defective herpes simplex virus type 1. J Natl Cancer Inst 1994; 86: 1209–1215.

    Article  CAS  PubMed  Google Scholar 

  133. Boviatsis EJ, Scharf JM, Chase M, Harrington K, Kowall NW, Breakefield XO et al. Antitumor activity and reporter gene transfer into rat brain neoplasms inoculated with herpes simplex virus vectors defective in thymidine kinase or ribonucleotide reductase. Gene Therapy 1994; 1: 323–331.

    CAS  PubMed  Google Scholar 

  134. Kaplitt MG, Tjuvajev JG, Leib DA, Berk J, Pettigrew KD, Posner JB et al. Mutant herpes simplex virus induced regression of tumors growing in immunocompetent rats. J Neurooncol 1994; 19: 137–147.

    Article  CAS  PubMed  Google Scholar 

  135. Valyi-Nagy T, Gesser RM, Raengsakulrach B, Deshmane SL, Randazzo BP, Dillner AJ et al. A thymidine kinase-negative HSV-1 strain establishes a persistent infection in SCID mice that features uncontrolled peripheral replication but only marginal nervous system involvement. Virology 1994; 199: 484–490.

    Article  CAS  PubMed  Google Scholar 

  136. Cameron JM, McDougall I, Marsden HS, Preston VG, Ryan DM, Subak-Sharpe JH . Ribonucleotide reductase encoded by herpes simplex virus is a determinant of the pathogenicity of the virus in mice and a valid antiviral target. J Gen Virol 1988; 69 (Part 10): 2607–2612.

    Article  CAS  PubMed  Google Scholar 

  137. Jacobson JG, Leib DA, Goldstein DJ, Bogard CL, Schaffer PA, Weller SK et al. A herpes simplex virus ribonucleotide reductase deletion mutant is defective for productive acute and reactivatable latent infections of mice and for replication in mouse cells. Virology 1989; 173: 276–283.

    Article  CAS  PubMed  Google Scholar 

  138. Mineta T, Rabkin SD, Martuza RL . Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant. Cancer Res 1994; 54: 3963–3966.

    CAS  PubMed  Google Scholar 

  139. Carroll NM, Chiocca EA, Takahashi K, Tanabe KK . Enhancement of gene therapy specificity for diffuse colon carcinoma liver metastases with recombinant herpes simplex virus. Ann Surg 1996; 224: 323–329; discussion 329–330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Yoon SS, Carroll NM, Chiocca EA, Tanabe KK . Cancer gene therapy using a replication-competent herpes simplex virus type 1 vector. Ann Surg 1998; 228: 366–374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Mineta T, Markert JM, Takamiya Y, Coen DM, Rabkin SD, Martuza RL . CNS tumor therapy by attenuated herpes simplex viruses. Gene Therapy 1994; 1 (Suppl 1): S78.

    PubMed  Google Scholar 

  142. Jacobs A, Tjuvajev JG, Dubrovin M, Akhurst T, Balatoni J, Beattie B et al. Positron emission tomography-based imaging of transgene expression mediated by replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in vivo. Cancer Res 2001; 61: 2983–2995.

    CAS  PubMed  Google Scholar 

  143. Kasuya H, Nishiyama Y, Nomoto S, Hosono J, Takeda S, Nakao A . Intraperitoneal delivery of hrR3 and ganciclovir prolongs survival in mice with disseminated pancreatic cancer. J Surg Oncol 1999; 72: 136–141.

    Article  CAS  PubMed  Google Scholar 

  144. Yoon SS, Nakamura H, Carroll NM, Bode BP, Chiocca EA, Tanabe KK . An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma. FASEB J 2000; 14: 301–311.

    Article  CAS  PubMed  Google Scholar 

  145. Pawlik TM, Nakamura H, Yoon SS, Mullen JT, Chandrasekhar S, Chiocca EA et al. Oncolysis of diffuse hepatocellular carcinoma by intravascular administration of a replication-competent, genetically engineered herpesvirus. Cancer Res 2000; 60: 2790–2795.

    CAS  PubMed  Google Scholar 

  146. Ikeda K, Wakimoto H, Ichikawa T, Jhung S, Hochberg FH, Louis DN et al. Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant. J Virol 2000; 74: 4765–4775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Spivack JG, Fareed MU, Valyi-Nagy T, Nash TC, O'Keefe JS, Gesser RM et al. Replication, establishment of latent infection, expression of the latency-associated transcripts and explant reactivation of herpes simplex virus type 1 gamma 34.5 mutants in a mouse eye model. J Gen Virol 1995; 76 (Part 2): 321–332.

    Article  CAS  PubMed  Google Scholar 

  148. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Kucharczuk JC, Randazzo B, Chang MY, Amin KM, Elshami AA, Sterman DH et al. Use of a ‘replication-restricted’ herpes virus to treat experimental human malignant mesothelioma. Cancer Res 1997; 57: 466–471.

    CAS  PubMed  Google Scholar 

  150. Randazzo BP, Bhat MG, Kesari S, Fraser NW, Brown SM . Treatment of experimental subcutaneous human melanoma with a replication-restricted herpes simplex virus mutant. J Invest Dermatol 1997; 108: 933–937.

    Article  CAS  PubMed  Google Scholar 

  151. Randazzo BP, Kesari S, Gesser RM, Alsop D, Ford JC, Brown SM et al. Treatment of experimental intracranial murine melanoma with a neuroattenuated herpes simplex virus 1 mutant. Virology 1995; 211: 94–101.

    Article  CAS  PubMed  Google Scholar 

  152. Kesari S, Randazzo BP, Valyi-Nagy T, Huang QS, Brown SM, MacLean AR et al. Therapy of experimental human brain tumors using a neuroattenuated herpes simplex virus mutant. Lab Invest 1995; 73: 636–648.

    CAS  PubMed  Google Scholar 

  153. Chambers R, Gillespie GY, Soroceanu L, Andreansky S, Chatterjee S, Chou J et al. Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a SCID mouse model of human malignant glioma. Proc Natl Acad Sci USA 1995; 92: 1411–1415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Lasner TM, Kesari S, Brown SM, Lee VM, Fraser NW, Trojanowski JQ . Therapy of a murine model of pediatric brain tumors using a herpes simplex virus type-1 ICP34.5 mutant and demonstration of viral replication within the CNS. J Neuropathol Exp Neurol 1996; 55: 1259–1269.

    Article  CAS  PubMed  Google Scholar 

  155. Andreansky SS, He B, Gillespie GY, Soroceanu L, Market J, Chou J et al. The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. Proc Natl Acad Sci USA 1996; 93: 11313–11318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Coukos G, Makrigiannakis A, Kang EH, Rubin SC, Albelda SM, Molnar-Kimber KL . Oncolytic herpes simplex virus-1 lacking ICP34.5 induces p53-independent death and is efficacious against chemotherapy-resistant ovarian cancer. Clin Cancer Res 2000; 6: 3342–3353.

    CAS  PubMed  Google Scholar 

  157. Lambright ES, Caparrelli DJ, Abbas AE, Toyoizumi T, Coukos G, Molnar-Kimber KL et al. Oncolytic therapy using a mutant type-1 herpes simplex virus and the role of the immune system. Ann Thorac Surg 1999; 68: 1756–1760; discussion 1761–1752.

    Article  CAS  PubMed  Google Scholar 

  158. 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.

    Article  CAS  PubMed  Google Scholar 

  159. 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.

    Article  CAS  PubMed  Google Scholar 

  160. Harrow S, Papanstassiou 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 Ther 2004; 11: 1648–1658.

    Article  CAS  PubMed  Google Scholar 

  161. Kesari S, Lasner TM, Balsara KR, Randazzo BP, Lee VM, Trojanowski JQ et al. A neuroattenuated ICP34.5-deficient herpes simplex virus type 1 replicates in ependymal cells of the murine central nervous system. J Gen Virol 1998; 79 (Part 3): 525–536.

    Article  CAS  PubMed  Google Scholar 

  162. McMenamin MM, Byrnes AP, Pike FG, Charlton HM, Coffin RS, Latchman DS et al. Potential and limitations of a gamma 34.5 mutant of herpes simplex 1 as a gene therapy vector in the CNS. Gene Therapy 1998; 5: 594–604.

    Article  CAS  PubMed  Google Scholar 

  163. Lasner TM, Tal-Singer R, Kesari S, Lee VM, Trojanowski JQ, Fraser NW . Toxicity and neuronal infection of a HSV-1 ICP34.5 mutant in nude mice. J Neurovirol 1998; 4: 100–105.

    Article  CAS  PubMed  Google Scholar 

  164. Pyles RB, Santoro IM, Groden J, Parysek LM . A novel multiply-mutated HSV-1 strain for the treatment of human brain tumors. Hum Gene Ther 1997; 8: 533–544.

    Article  CAS  PubMed  Google Scholar 

  165. Kramm CM, Chase M, Herrlinger U, Jacobs A, Pechan PA, Rainov NG et al. Therapeutic efficiency and safety of a second-generation replication-conditional HSV1 vector for brain tumor gene therapy. Hum Gene Ther 1997; 8: 2057–2068.

    Article  CAS  PubMed  Google Scholar 

  166. Mineta T, Rabkin SD, Yazaki T, Hunter WD, Martuza RL . Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med 1995; 1: 938–943.

    Article  CAS  PubMed  Google Scholar 

  167. Hunter WD, Martuza RL, Feigenbaum F, Todo T, Mineta T, Yazaki T et al. Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation of intracerebral injection in nonhuman primates. J Virol 1999; 73: 6319–6326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Sundaresan P, Hunter WD, Martuza RL, Rabkin SD . Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation in mice. J Virol 2000; 74: 3832–3841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Todo T, Feigenbaum F, Rabkin SD, Lakeman F, Newsome JT, Johnson PA et al. Viral shedding and biodistribution of G207, a multimutated, conditionally replicating herpes simplex virus type 1, after intracerebral inoculation in aotus. Mol Ther 2000; 2: 588–595.

    Article  CAS  PubMed  Google Scholar 

  170. Varghese S, Newsome JT, Rabkin SD, McGeagh K, Mahoney D, Nielsen P et al. Preclinical safety evaluation of G207, a replication-competent herpes simplex virus type 1, inoculated intraprostatically in mice and nonhuman primates. Hum Gene Ther 2001; 12: 999–1010.

    Article  CAS  PubMed  Google Scholar 

  171. Kooby DA, Carew JF, Halterman MW, Mack JE, Bertino JR, Blumgart LH et al. Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207). FASEB J 1999; 13: 1325–1334.

    Article  CAS  PubMed  Google Scholar 

  172. Toda M, Rabkin SD, Kojima H, Martuza RL . Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity. Hum Gene Ther 1999; 10: 385–393.

    Article  CAS  PubMed  Google Scholar 

  173. Bennett JJ, Kooby DA, Delman K, McAuliffe P, Halterman MW, Federoff H et al. Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer. J Mol Med 2000; 78: 166–174.

    Article  CAS  PubMed  Google Scholar 

  174. Coukos G, Makrigiannakis A, Montas S, Kaiser LR, Toyozumi T, Benjamin I et al. Multi-attenuated herpes simplex virus-1 mutant G207 exerts cytotoxicity against epithelial ovarian cancer but not normal mesothelium and is suitable for intraperitoneal oncolytic therapy. Cancer Gene Ther 2000; 7: 275–283.

    Article  CAS  PubMed  Google Scholar 

  175. Blank SV, Rubin SC, Coukos G, Amin KM, Albelda SM, Molnar-Kimber KL . Replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation. Hum Gene Ther 2002; 13: 627–639.

    Article  CAS  PubMed  Google Scholar 

  176. Varghese S, Rabkin SD . Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Ther 2002; 9: 967–978.

    Article  CAS  PubMed  Google Scholar 

  177. Iizuka Y, Suzuki A, Kawakami Y, Toda M . Augmentation of antitumor immune responses by multiple intratumoral inoculations of replication-conditional HSV and interleukin-12. J Immunother 2004; 27: 92–98.

    Article  CAS  PubMed  Google Scholar 

  178. Chahlavi A, Rabkin S, Todo T, Sundaresan P, Martuza R . Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice. Gene Therapy 1999; 6: 1751–1758.

    Article  CAS  PubMed  Google Scholar 

  179. Delman KA, Bennett JJ, Zager JS, Burt BM, McAuliffe PF, Petrowsky H et al. Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy. Hum Gene Ther 2000; 11: 2465–2472.

    Article  CAS  PubMed  Google Scholar 

  180. Todo T, Rabkin SD, Sundaresan P, Wu A, Meehan KR, Herscowitz HB et al. Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus. Hum Gene Ther 1999; 10: 2741–2755.

    Article  CAS  PubMed  Google Scholar 

  181. Toda M, Iizuka Y, Kawase T, Uyemura K, Kawakami Y . Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV. Cancer Gene Ther 2002; 9: 356–364.

    Article  CAS  PubMed  Google Scholar 

  182. Endo T, Toda M, Watanabe M, Iizuka Y, Kubota T, Kitajima M et al. In situ cancer vaccination with a replication-conditional HSV for the treatment of liver metastasis of colon cancer. Cancer Gene Ther 2002; 9: 142–148.

    Article  CAS  PubMed  Google Scholar 

  183. Toda M . Immuno-viral therapy as a new approach for the treatment of brain tumors. Drug News Perspect 2003; 16: 223–229.

    Article  CAS  PubMed  Google Scholar 

  184. 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.

    Article  CAS  PubMed  Google Scholar 

  185. Meignier B, Longnecker R, Roizman B . In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020: construction and evaluation in rodents. J Infect Dis 1988; 158: 602–614.

    Article  CAS  PubMed  Google Scholar 

  186. Meignier B, Martin B, Whitley RJ, Roizman B . In vivo behavior of genetically engineered herpes simplex viruses R7017 and R7020. II. Studies in immunocompetent and immunosuppressed owl monkeys (Aotus trivirgatus). J Infect Dis 1990; 162: 313–321.

    Article  CAS  PubMed  Google Scholar 

  187. Advani SJ, Chung SM, yan SY, Gillespie GY, Markert JM, Whitley RJ et al. Replication-competent, nonneuroinvasive genetically engineered herpes virus is highly effective in the treatment of therapy-resistant experimental human tumors. Cancer Res 1999; 59: 2055–2058.

    CAS  PubMed  Google Scholar 

  188. Chung SM, Advani SJ, Bradley JD, Kataoka Y, Vashistha K, Yan SY et al. The use of a genetically engineered herpes simplex virus (R7020) with ionizing radiation for experimental hepatoma. Gene Therapy 2002; 9: 75–80.

    Article  CAS  PubMed  Google Scholar 

  189. McAuliffe PF, Jarnagin WR, Johnson P, Delman KA, Federoff H, Fong Y . Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses. J Gastrointest Surg 2000; 4: 580–588.

    Article  CAS  PubMed  Google Scholar 

  190. Cozzi PJ, Malhotra S, McAuliffe P, Kooby DA, Federoff HJ, Huryk B et al. Intravesical oncolytic viral therapy using attenuated, replication-competent herpes simplex viruses G207 and Nv1020 is effective in the treatment of bladder cancer in an orthotopic syngeneic model. FASEB J 2001; 15: 1306–1308.

    Article  CAS  PubMed  Google Scholar 

  191. Cozzi PJ, Burke PB, Bhargav A, Heston WD, Huryk B, Scardino PT et al. Oncolytic viral gene therapy for prostate cancer using two attenuated, replication-competent, genetically engineered herpes simplex viruses. Prostate 2002; 53: 95–100.

    Article  CAS  PubMed  Google Scholar 

  192. Bennett JJ, Delman KA, Burt BM, Mariotti A . Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer. Cancer Gene Ther 2002; 9: 935–945.

    Article  CAS  PubMed  Google Scholar 

  193. Delman KA, Zager JS, Bhargava A, Petrowsky H, Malhotra S, Ebright MI et al. Effect of murine liver cell proliferation on herpes viral behavior: implications for oncolytic viral therapy. Hepatology 2004; 39: 1525–1532.

    Article  CAS  PubMed  Google Scholar 

  194. Fong Y, Kemeny N, Jarnagin W, Stanziale S, Guilfoyle B, Susani N et al. Phase 1 study of a replication-competent herpes simplex oncolytic virus for treatment of hepatic colorectal metastases. ASCO Annual Meeting 2002.

  195. 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 

  196. Chung RY, Saeki Y, Chiocca EA . B-myb promoter retargeting of herpes simplex virus gamma34.5 gene-mediated virulence toward tumor and cycling cells. J Virol 1999; 73: 7556–7564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Bennett JD, Farlie PG, Watson RJ . E2F binding is required but not sufficient for repression of B-myb transcription in quiescent fibroblasts. Oncogene 1996; 13: 1073–1082.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Hinoda Y, Ikematsu Y, Horinochi M, Sato S, Yamamoto K, Nakano T et al. Increased expression of MUC1 in advanced pancreatic cancer. J Gastroenterol 2003; 38: 1162–1166.

    Article  CAS  PubMed  Google Scholar 

  200. Mullen JT, Kasuya H, Yoon SS, Carroll NM, Pawlik TM, Chandrasekhar S et al. Regulation of herpes simplex virus 1 replication using tumor-associated promoters. Ann Surg 2002; 236: 502–512; discussion 512–503.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Kasuya H, Pawlik TM, Mullen JT, Donahue JM, Nakamura H, Chandrasekhar S et al. Selectivity of an oncolytic herpes simplex virus for cells expressing the DF3/MUC1 antigen. Cancer Res 2004; 64: 2561–2567.

    Article  CAS  PubMed  Google Scholar 

  202. Miyatake S, Iyer A, Martuza RL, Rabkin SD . Transcriptional targeting of herpes simplex virus for cell-specific replication. J Virol 1997; 71: 5124–5132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Miyatake S . Gene therapy using tissue-specific replication competent HSV. Hum Cell 2002; 15: 130–137.

    Article  PubMed  Google Scholar 

  204. Yamamura H, Hashio M, Noguchi M, Sugenoya Y, Osakada M, Hirano N et al. Identification of the transcriptional regulatory sequences of human calponin promoter and their use in targeting a conditionally replicating herpes vector to malignant human soft tissue and bone tumors. Cancer Res 2001; 61: 3969–3977.

    CAS  PubMed  Google Scholar 

  205. Everts M, Curiel DT . Transductional targeting of adenoviral cancer gene therapy. Curr Gene Ther 2004; 4: 337–346.

    Article  CAS  PubMed  Google Scholar 

  206. Laquerre S, Anderson DB, Stolz DB, Glorioso JC . Recombinant herpes simplex virus type 1 engineered for targeted binding to erythropoietin receptor-bearing cells. J Virol 1998; 72: 9683–9697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Argnani R, Boccafogli L, Marconi PC, Manservigi R . Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide. Gene Therapy 2004; 11: 1087–1098.

    Article  CAS  PubMed  Google Scholar 

  208. Zhou G, Ye GJ, Debinski W, Roizman B . Engineered herpes simplex virus 1 is dependent on IL13Ralpha 2 receptor for cell entry and independent of glycoprotein D receptor interaction. Proc Natl Acad Sci USA 2002; 99: 15124–15129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Ford AC, Grandis JR . Targeting epidermal growth factor receptor in head and neck cancer. Head Neck 2003; 25: 67–73.

    Article  PubMed  Google Scholar 

  210. Gosselin MA, Lee RJ . Folate receptor-targeted liposomes as vectors for therapeutic agents. Biotechnol Annu Rev 2002; 8: 103–131.

    Article  CAS  PubMed  Google Scholar 

  211. Assimakopoulos D, Kolettas E, Patrikakos G, Evangelou A . The role of CD44 in the development and prognosis of head and neck squamous cell carcinomas. Histol Histopathol 2002; 17: 1269–1281.

    CAS  PubMed  Google Scholar 

  212. Mullen JT, Donahue JM, Chandrasekhar S, Yoon SS, Liu W, Ellis LM et al. Oncolysis by viral replication and inhibition of angiogenesis by a replication-conditional herpes simplex virus that expresses mouse endostatin. Cancer 2004; 101: 869–877.

    Article  CAS  PubMed  Google Scholar 

  213. Andreansky S, He B, van Cott J, McGhee J, Market JM, Gillespie GY et al. Treatment of intracranial gliomas in immunocompetent mice using herpes simplex viruses that express murine interleukins. Gene Therapy 1998; 5: 121–130.

    Article  CAS  PubMed  Google Scholar 

  214. Parker JN, Gillespie GY, Love CE, Randall S, Whitley RJ, Markert JM . Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors. Proc Natl Acad Sci USA 2000; 97: 2208–2213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Bennett JJ, Malhotra S, Wong RJ, Delman K, Zager J, St-Louis M et al. Interleukin 12 secretion enhances antitumor efficacy of oncolytic herpes simplex viral therapy for colorectal cancer. Ann Surg 2001; 233: 819–826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Jarnagin WR, Zager JS, Klimstra D, Delman KA, Malhotra S, Elbright M et al. Neoadjuvant treatment of hepatic malignancy: an oncolytic herpes simplex virus expressing IL-12 effectively treats the parent tumor and protects against recurrence-after resection. Cancer Gene Ther 2003; 10: 215–223.

    Article  CAS  PubMed  Google Scholar 

  217. Wong RJ, Chan MK, Yu Z, Kim TH, Bhargava A, Stiles BM et al. Effective intravenous therapy of murine pulmonary metastases with an oncolytic herpes virus expressing interleukin 12. Clin Cancer Res 2004; 10: 251–259.

    Article  CAS  PubMed  Google Scholar 

  218. Wong RJ, Chan MK, Yu Z, Ghossein RA, Ngai I, Adusumilli PS et al. Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12. Clin Cancer Res 2004; 10: 4509–4516.

    Article  CAS  PubMed  Google Scholar 

  219. Wong RJ, Patel SG, Kim S, DeMatteo RP, Malhotra S, Bennett JJ et al. Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma. Hum Gene Ther 2001; 12: 253–265.

    Article  CAS  PubMed  Google Scholar 

  220. Carew JF, Kooby DA, Halterman MW, Kim SH, Federoff HJ, Fong Y . A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes. Mol Ther 2001; 4: 250–256.

    Article  CAS  PubMed  Google Scholar 

  221. Zager JS, Delman KA, Malhotra S, Ebright MI, Bennett JJ, Kates T et al. Combination vascular delivery of herpes simplex oncolytic viruses and amplicon mediated cytokine gene transfer is effective therapy for experimental liver cancer. Mol Med 2001; 7: 561–568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Therapy 2003; 10: 292–303.

    Article  CAS  PubMed  Google Scholar 

  223. Coffin RS, Liu B, Han Z, Simpson G, Hu J, Coombes C et al. OncoVEX: A family of oncolytic herpes simplex viruses optimised for therapeutic use. ASCO Annual Meeting: Orlando, FL. 2004.

  224. Nakamura H, Mullen JT, Chandrasekhar S, Pawlik TM, Yoon SS, Tanabe KK . Multimodality therapy with a replication-conditional herpes simplex virus 1 mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5-fluorocytosine to 5-fluorouracil. Cancer Res 2001; 61: 5447–5452.

    CAS  PubMed  Google Scholar 

  225. Chase M, Chung RY, Chiocca EA . An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy. Nat Biotechnol 1998; 16: 444–448.

    Article  CAS  PubMed  Google Scholar 

  226. Ichikawa T, Petros WP, Ludeman SM, Fangmeier J, Hochberg FH, Colvin OM et al. Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral bioconversion by a replicating oncolytic viral vector. Cancer Res 2001; 61: 864–868.

    CAS  PubMed  Google Scholar 

  227. Pawlik TM, Nakamura H, Mullen JT, Kasuya H, Yoon SS, Chandrasekhar S et al. Prodrug bioactivation and oncolysis of diffuse liver metastases by a herpes simplex virus 1 mutant that expresses the CYP2B1 transgene. Cancer 2002; 95: 1171–1181.

    Article  CAS  PubMed  Google Scholar 

  228. Aghi M, Chou TC, Suling K, Breakefield XO, Chiocca EA . Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P450 2B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies. Cancer Res 1999; 59: 3861–3865.

    CAS  PubMed  Google Scholar 

  229. Cinatl Jr J, Cinatl J, Michaelis M, Kabickova H, Kotchetkov R, Vogel JU et al. Potent oncolytic activity of multimutated herpes simplex virus G207 in combination with vincristine against human rhabdomyosarcoma. Cancer Res 2003; 63: 1508–1514.

    CAS  PubMed  Google Scholar 

  230. Bennett JJ, Adusumilli P, Petrowsky H, Burt BM, Roberts G, Delman KA et al. Up-regulation of GADD34 mediates the synergistic anticancer activity of mitomycin C and a gamma134.5 deleted oncolytic herpes virus (G207). FASEB J 2004; 18: 1001–1003.

    Article  CAS  PubMed  Google Scholar 

  231. Post DE, Fulci G, Chiocca EA, Van Meir EG . Replicative oncolytic herpes simplex viruses in combination cancer therapies. Curr Gene Ther 2004; 4: 41–51.

    Article  CAS  PubMed  Google Scholar 

  232. Stanziale SF, Petrowsky H, Joe JK, Roberts GD, Zager JS, Gusani NJ et al. Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase. Surgery 2002; 132: 353–359.

    Article  PubMed  Google Scholar 

  233. Toyoizumi T, Mick R, Abbas AE, Kang EH, Kaiser LR, Molnar-Kimber KL . Combined therapy with chemotherapeutic agents and herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) in human non-small cell lung cancer. Hum Gene Ther 1999; 10: 3013–3029.

    Article  CAS  PubMed  Google Scholar 

  234. Spear MA, Sun F, Eling DJ, Gilpin E, Kipps TJ, Chiocca EA et al. Cytotoxicity, apoptosis, and viral replication in tumor cells treated with oncolytic ribonucleotide reductase-defective herpes simplex type 1 virus (hrR3) combined with ionizing radiation. Cancer Gene Ther 2000; 7: 1051–1059.

    Article  CAS  PubMed  Google Scholar 

  235. Advani SJ, Sibley GS, Song PY, Hallahan DE, Kataoka Y, Roizman B et al. Enhancement of replication of genetically engineered herpes simplex viruses by ionizing radiation: a new paradigm for destruction of therapeutically intractable tumors. Gene Therapy 1998; 5: 160–165.

    Article  CAS  PubMed  Google Scholar 

  236. Bradley JD, Kataoka Y, Advani S, Chung SM, Arani RB, Gillespie GY et al. Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus. Clin Cancer Res 1999; 5: 1517–1522.

    CAS  PubMed  Google Scholar 

  237. Jorgensen TJ, Katz S, Wittmack EK, Varghese S, Todo T, Rabkin SD et al. Ionizing radiation does not alter the antitumor activity of herpes simplex virus vector G207 in subcutaneous tumor models of human and murine prostate cancer. Neoplasia 2001; 3: 451–456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Wang Q, Guo J, Jia W . Intracerebral recombinant HSV-1 vector does not reactivate latent HSV-1. Gene Therapy 1997; 4: 1300–1304.

    Article  CAS  PubMed  Google Scholar 

  239. Speck PG, Efstathiou S, Minson AC . In vivo complementation studies of a glycoprotein H-deleted herpes simplex virus-based vector. J Gen Virol 1996; 77 (Part 10): 2563–2568.

    Article  CAS  PubMed  Google Scholar 

  240. Villarreal EC . Current and potential therapies for the treatment of herpes-virus infections. Prog Drug Res 2003; 60: 263–307.

    Article  CAS  PubMed  Google Scholar 

  241. Gatto B . Monoclonal antibodies in cancer therapy. Curr Med Chem Anti-Cancer Agents 2004; 4: 411–414.

    Article  CAS  PubMed  Google Scholar 

  242. Taneja S, MacGregor J, Markus S, Ha S, Mohr I . Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells. Proc Natl Acad Sci USA 2001; 98: 8804–8808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Yan W, Kitzes G, Dormishian F, Hawkins L, Sampson-Johannes A, Watanabe J et al. Developing novel oncolytic adenoviruses through bioselection. J Virol 2003; 77: 2640–2650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. MacKie RM, Stewart B, Brown SM . Intralesional injection of herpes simplex virus 1716 in metastatic melanoma. Lancet 2001; 357: 525–526.

    Article  CAS  PubMed  Google Scholar 

  245. Andreansky S, Soroceanu L, flotte ER, Chou J, Markert JM, Gillespie GY et al. Evaluation of genetically engineered herpes simplex viruses as oncolytic agents for human malignant brain tumors. Cancer Res 1997; 57: 1502–1509.

    CAS  PubMed  Google Scholar 

  246. Nakao A, Kimata H, Imai T, Kikumori T, Teshigahara O, Nagasaka T et al. Intratumoral injection of herpes simplex virus HF10 in recurrent breast cancer. Ann Oncol 2004; 15: 988–989.

    Article  CAS  PubMed  Google Scholar 

  247. Takakuwa H, Goshima F, Nozawa N, Yoshikawa T, Kimata H, Nakao A et al. Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent mice. Arch Virol 2003; 148: 813–825.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We extend special thanks to Dr Sylvie Laquerre (ViroPharma, Inc., Exton, PA) for her critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Mary Crowley Medical Research Center, Dallas, TX, USA

    Y Shen & J Nemunaitis

Authors
  1. Y Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Nemunaitis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Nemunaitis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shen, Y., Nemunaitis, J. Herpes simplex virus 1 (HSV-1) for cancer treatment. Cancer Gene Ther 13, 975–992 (2006). https://doi.org/10.1038/sj.cgt.7700946

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700946

Keywords

This article is cited by

Search

Advanced search

Quick links