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Construction and Characterization of an Oncolytic HSV Vector Containing a Fusogenic Glycoprotein and Prodrug Activation for Enhanced Local Tumor Control

  • Guy R. SimpsonEmail author
  • Robert S. Coffin
Protocol
Part of the Methods in Molecular Biology™ book series (MIMB, volume 542)

Summary

A large number of oncolytic viral vectors are currently under clinical development for cancer therapy. Herpes simplex virus type 1 (HSV-1) has demonstrated particular promise in this field, showing genetically engineered selective tumor replication and cytotoxicity in a wide variety of tumor types, without damaging healthy tissues. Enhanced activity has been observed when a range of therapeutic genes has been inserted into various oncolytic HSV genomes. Here, we discuss methods used to develop and characterize an oncolytic HSV virus that combines expression of a highly potent prodrug activating gene (yeast cytosine deaminase/uracil phosphoribosyltransferase fusion [Fcy::Fur]) and the fusogenic glycoprotein from gibbon ape leukemia virus (GALV) for enhanced local tumor control.

Key Words

Cancer therapy fusogenic membrane glycoproteins (FMG) herpes simplex virus type 1 (HSV-1) oncolytic, prodrug activation therapy 

Notes

Acknowledgement

We thank Dr. Georgina Platt and Marianna Anesti for advice and proofreading of the chapter.

References

  1. 1.
    Ring CJ. (2002) Cytolytic viruses as potential anti-cancer agents. J Gen Virol 83:491–502.PubMedGoogle Scholar
  2. 2.
    Coffey MC, Strong JE, Forsyth PA, Lee PW. (1998) Reovirus therapy of tumors with activated Ras pathway. Science 282:1332–1334.PubMedCrossRefGoogle Scholar
  3. 3.
    MacLean A, Robertson L, McKay E, Brown SM. (1991) The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency. J Gen Virol 72:2305–2310.PubMedCrossRefGoogle Scholar
  4. 4.
    Bolovan CA, Sawtell NM, Thompson RL. (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.PubMedGoogle Scholar
  5. 5.
    Mineta T, Rabkin SD, Yazaki T, Hunter WD, Martuza RL. (1995) Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med 1:938–943.PubMedCrossRefGoogle Scholar
  6. 6.
    Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff DD, Kirn DH. (1997) ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 3:639–645.PubMedCrossRefGoogle Scholar
  7. 7.
    Pawelek JM, Low KB, Bermudes D. (1997) Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res 57:4537–4544.PubMedGoogle Scholar
  8. 8.
    Clemens MJ. (1997) PKR—a protein kinase regulated by double-stranded RNA. Int J Biochem Cell Biol 29:945–949.PubMedCrossRefGoogle Scholar
  9. 9.
    Roizman B, Markovitz N. (1997) Herpes simplex virus virulence: the functions of the gamma (1)34.5 gene. J Neurovirol 3(Suppl 1):S1–S2.PubMedGoogle Scholar
  10. 10.
    He B, Chou J, Brandimarti R, Mohr I, Gluzman Y, Roizman B. (1997) Suppression of the phenotype of gamma(1)34.5- herpes simplex virus 1: failure of activated RNA-dependent protein kinase to shut off protein synthesis is associated with a deletion in the domain of the alpha47 gene. J Virol 71:6049–6054.PubMedGoogle Scholar
  11. 11.
    Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D et al. (2000) Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther 7:859–866.PubMedCrossRefGoogle Scholar
  12. 12.
    Andreansky SS, He B, Gillespie GY, Soroceanu L, Markert J, Chou J et al. (1996) The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. Proc Natl Acad Sci USA 93:11313–11318.PubMedCrossRefGoogle Scholar
  13. 13.
    Jennings SR, Rice PL, Kloszewski ED, Anderson RW, Thompson DL, Tevethia SS. (1985) Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells. J Virol 56:757–766.PubMedGoogle Scholar
  14. 14.
    Hill AB, Barnett BC, McMichael AJ, McGeoch DJ. (1994) HLA class I molecules are not transported to the cell surface in cells infected with herpes simplex virus types 1 and 2. J Immunol 152:2736–2741.PubMedGoogle Scholar
  15. 15.
    Mohr I, Gluzman Y. (1996) A herpesvirus genetic element which affects translation in the absence of the viral GADD34 function. EMBO J 15:4759–4766.PubMedGoogle Scholar
  16. 16.
    Cassady KA, Gross M, Roizman B. (1998) The second-site mutation in the herpes simplex virus recombinants lacking the gamma134.5 genes precludes shutoff of protein synthesis by blocking the phosphorylation of eIF-2alpha. J Virol 72:7005–7011.PubMedGoogle Scholar
  17. 17.
    Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P et al. (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 10:292–303.PubMedCrossRefGoogle Scholar
  18. 18.
    Hu JC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ et al. (2006) A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res 12:6737–6747.PubMedCrossRefGoogle Scholar
  19. 19.
    Bateman A, Bullough F, Murphy S, Emiliusen L, Lavillette D, Cosset FL et al. (2000) Fusogenic membrane glycoproteins as a novel class of genes for the local and immune-mediated control of tumor growth. Cancer Res 60:1492–1497.PubMedGoogle Scholar
  20. 20.
    Galanis E, Bateman A, Johnson K, Diaz RM, James CD, Vile R et al. (2001) Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas. Hum Gene Ther 12:811–821.PubMedCrossRefGoogle Scholar
  21. 21.
    Diaz RM, Bateman A, Emiliusen L, Fielding A, Trono D, Russell SJ et al. (2000) A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy. Gene Ther 7:1656–1663.PubMedCrossRefGoogle Scholar
  22. 22.
    Fu X, Tao L, Jin A, Vile R, Brenner MK, Zhang X. (2003) Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect. Mol Ther 7:748–754.PubMedCrossRefGoogle Scholar
  23. 23.
    Tiraby M, Cazaux C, Baron M, Drocourt D, Reynes JP, Tiraby G. (1998) Concomitant expression of E. coli cytosine deaminase and uracil phosphoribosyltransferase improves the cytotoxicity of 5-fluorocytosine. FEMS Microbiol Lett 167:41–49.Google Scholar
  24. 24.
    Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM. (1991) Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252:854–856.PubMedCrossRefGoogle Scholar
  25. 25.
    McKie EA, MacLean AR, Lewis AD, Cruickshank G, Rampling R, Barnett SC et al. (1996) 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 74:745–752.PubMedCrossRefGoogle Scholar
  26. 26.
    Todo T, Martuza RL, Rabkin SD, Johnson PA. (2001) Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci USA 98:6396–6401.PubMedCrossRefGoogle Scholar
  27. 27.
    Roizman B, Jenkins FJ. (1985) Genetic engineering of novel genomes of large DNA viruses. Science 229:1208–1214.PubMedCrossRefGoogle Scholar
  28. 28.
    Simpson GR, Han Z, Liu B, Wang Y, Campbell G, Coffin RS. (2006) Combination of a fusogenic glycoprotein, prodrug activation, and oncolytic herpes simplex virus for enhanced local tumor control. Cancer Res 66:4835–4842.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Oncology, Postgraduate Medical SchoolUniversity of SurreyUK
  2. 2.Biovex, Inc.Woburn

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