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. 2000 Jul 3;83(3):329–332. doi: 10.1054/bjoc.2000.1346

Specific oncolytic activity of herpesvirus saimiri in pancreatic cancer cells

A J Stevenson 1, M S Giles 1, K T Hall 1, D J Goodwin 1, M A Calderwood 1, A F Markham 1, A Whitehouse 1
PMCID: PMC2374565  PMID: 10917547

Abstract

The potential use of oncolytic viruses in the treatment of cancer has been investigated for some time. A variety of agents have been studied, including some which appear to be selectively replication-competent in cancer cell lines. In this study, we have investigated the ability of herpesvirus saimiri to specifically lyse selected human cancer cell lines. Upon infection with a replication-competent virus carrying the EGFP reporter gene and a neomycin resistance marker, the pancreatic cancer lines MIAPACA and PANC-1 exhibited definite cytopathic effects. In contrast, the colonic carcinoma cell lines SW480 and HCT116 were phenotypically unaltered. In addition, stable cell lines could not be generated from PANC-1 infected cultures, in marked contrast to cultures of cells from other human tissues. Virus recovery assays demonstrated that all of the cell lines produced a small amount of virus post-infection, but that virus replication was minimal after 1 week in culture. In addition, treatment with acyclovir inhibited virus replication but paradoxically increased cytopathic effect. These data suggest that herpesvirus saimiri may have potential as an oncolytic agent for the treatment of pancreatic cancer. © 2000 Cancer Research Campaign

Keywords: pancreatic cancer, oncolytic, gene therapy, HVS

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Selected References

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  1. Arai H., Gordon D., Nabel E. G., Nabel G. J. Gene transfer of Fas ligand induces tumor regression in vivo. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13862–13867. doi: 10.1073/pnas.94.25.13862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biesinger B., Müller-Fleckenstein I., Simmer B., Lang G., Wittmann S., Platzer E., Desrosiers R. C., Fleckenstein B. Stable growth transformation of human T lymphocytes by herpesvirus saimiri. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3116–3119. doi: 10.1073/pnas.89.7.3116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bischoff J. R., Kirn D. H., Williams A., Heise C., Horn S., Muna M., Ng L., Nye J. A., Sampson-Johannes A., Fattaey A. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996 Oct 18;274(5286):373–376. doi: 10.1126/science.274.5286.373. [DOI] [PubMed] [Google Scholar]
  4. Culver K. W., Ram Z., Wallbridge S., Ishii H., Oldfield E. H., Blaese R. M. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science. 1992 Jun 12;256(5063):1550–1552. doi: 10.1126/science.1317968. [DOI] [PubMed] [Google Scholar]
  5. Desrosiers R. C., Bakker A., Kamine J., Falk L. A., Hunt R. D., King N. W. A region of the Herpesvirus saimiri genome required for oncogenicity. Science. 1985 Apr 12;228(4696):184–187. doi: 10.1126/science.2983431. [DOI] [PubMed] [Google Scholar]
  6. Desrosiers R. C., Burghoff R. L., Bakker A., Kamine J. Construction of replication-competent Herpesvirus saimiri deletion mutants. J Virol. 1984 Feb;49(2):343–348. doi: 10.1128/jvi.49.2.343-348.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Desrosiers R. C., Silva D. P., Waldron L. M., Letvin N. L. Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization. J Virol. 1986 Feb;57(2):701–705. doi: 10.1128/jvi.57.2.701-705.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elion G. B. The chemotherapeutic exploitation of virus-specified enzymes. Adv Enzyme Regul. 1980;18:53–66. doi: 10.1016/0065-2571(80)90008-4. [DOI] [PubMed] [Google Scholar]
  9. Grassmann R., Fleckenstein B. Selectable recombinant herpesvirus saimiri is capable of persisting in a human T-cell line. J Virol. 1989 Apr;63(4):1818–1821. doi: 10.1128/jvi.63.4.1818-1821.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heise C. C., Williams A., Olesch J., Kirn D. H. Efficacy of a replication-competent adenovirus (ONYX-015) following intratumoral injection: intratumoral spread and distribution effects. Cancer Gene Ther. 1999 Nov-Dec;6(6):499–504. doi: 10.1038/sj.cgt.7700071. [DOI] [PubMed] [Google Scholar]
  11. Heise C., Sampson-Johannes A., Williams A., McCormick F., Von Hoff D. D., Kirn D. H. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med. 1997 Jun;3(6):639–645. doi: 10.1038/nm0697-639. [DOI] [PubMed] [Google Scholar]
  12. Johnson P. A., Wang M. J., Friedmann T. Improved cell survival by the reduction of immediate-early gene expression in replication-defective mutants of herpes simplex virus type 1 but not by mutation of the virion host shutoff function. J Virol. 1994 Oct;68(10):6347–6362. doi: 10.1128/jvi.68.10.6347-6362.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koomey J. M., Mulder C., Burghoff R. L., Fleckenstein B., Desrosiers R. C. Deletion of DNA sequence in a nononcogenic variant of Herpesvirus saimiri. J Virol. 1984 May;50(2):662–665. doi: 10.1128/jvi.50.2.662-665.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Medveczky M. M., Szomolanyi E., Hesselton R., DeGrand D., Geck P., Medveczky P. G. Herpesvirus saimiri strains from three DNA subgroups have different oncogenic potentials in New Zealand white rabbits. J Virol. 1989 Sep;63(9):3601–3611. doi: 10.1128/jvi.63.9.3601-3611.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Medveczky P., Szomolanyi E., Desrosiers R. C., Mulder C. Classification of herpesvirus saimiri into three groups based on extreme variation in a DNA region required for oncogenicity. J Virol. 1984 Dec;52(3):938–944. doi: 10.1128/jvi.52.3.938-944.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  17. Rampling R., Cruickshank G., MacLean A., Brown M. Therapeutic replication-competent herpes virus. Nat Med. 1998 Feb;4(2):133–133. doi: 10.1038/nm0298-133c. [DOI] [PubMed] [Google Scholar]
  18. Redston M. S., Caldas C., Seymour A. B., Hruban R. H., da Costa L., Yeo C. J., Kern S. E. p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res. 1994 Jun 1;54(11):3025–3033. [PubMed] [Google Scholar]
  19. Roth J. A., Cristiano R. J. Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst. 1997 Jan 1;89(1):21–39. doi: 10.1093/jnci/89.1.21. [DOI] [PubMed] [Google Scholar]
  20. Sandig V., Brand K., Herwig S., Lukas J., Bartek J., Strauss M. Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death. Nat Med. 1997 Mar;3(3):313–319. doi: 10.1038/nm0397-313. [DOI] [PubMed] [Google Scholar]
  21. Simmer B., Alt M., Buckreus I., Berthold S., Fleckenstein B., Platzer E., Grassmann R. Persistence of selectable herpesvirus saimiri in various human haematopoietic and epithelial cell lines. J Gen Virol. 1991 Aug;72(Pt 8):1953–1958. doi: 10.1099/0022-1317-72-8-1953. [DOI] [PubMed] [Google Scholar]
  22. Stevenson A. J., Cooper M., Griffiths J. C., Gibson P. C., Whitehouse A., Jones E. F., Markham A. F., Kinsey S. E., Meredith D. M. Assessment of Herpesvirus saimiri as a potential human gene therapy vector. J Med Virol. 1999 Mar;57(3):269–277. [PubMed] [Google Scholar]

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