Skip to main content

Construction of Oncolytic Herpes Simplex Virus with Therapeutic Genes of Interest

  • Protocol
  • First Online:
Viral Vectors for Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1937))

Abstract

Herpes simplex virus (HSV) is one of the most extensively studied oncolytic virus platforms. The recent FDA approval of talimogene laherparepvec (T-VEC) has been accelerating translational research of oncolytic HSV (oHSV) as a promising therapeutic for refractory cancers such as glioblastoma, the deadliest primary malignancy in the brain. The large genome size of HSV readily allows arming of oHSV by incorporating therapeutic transgenes within the virus, as exemplified by T-VEC carrying GM-CSF, thereby enhancing the anticancer activity of oHSV. Here we describe a bacterial artificial chromosome-based method for construction of an oHSV expressing a transgene, which we routinely use in the laboratory to create a number of different recombinant oHSV bearing either therapeutic or reporter genes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ott PA, Hodi FS (2016) Talimogene laherparepvec for the treatment of advanced melanoma. Clin Cancer Res 22(13):3127–3131. https://doi.org/10.1158/1078-0432.CCR-15-2709

    Article  CAS  PubMed  Google Scholar 

  2. Peters C, Rabkin SD (2015) Designing herpes viruses as oncolytics. Mol Ther Oncolytics 2:15010. https://doi.org/10.1038/mto.2015.10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kaur B, Cripe TP, Chiocca EA (2009) “Buy one get one free”: armed viruses for the treatment of cancer cells and their microenvironment. Curr Gene Ther 9(5):341–355

    Article  CAS  Google Scholar 

  4. Kuroda T, Martuza RL, Todo T et al (2006) Flip-Flop HSV-BAC: bacterial artificial chromosome based system for rapid generation of recombinant herpes simplex virus vectors using two independent site-specific recombinases. BMC Biotechnol 6:40. https://doi.org/10.1186/1472-6750-6-40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kuroda T, Rabkin SD, Martuza RL (2006) Effective treatment of tumors with strong beta-catenin/T-cell factor activity by transcriptionally targeted oncolytic herpes simplex virus vector. Cancer Res 66(20):10127–10135. https://doi.org/10.1158/0008-5472.CAN-06-2744

    Article  CAS  PubMed  Google Scholar 

  6. Dmitrieva N, Yu L, Viapiano M et al (2011) Chondroitinase ABC I-mediated enhancement of oncolytic virus spread and antitumor efficacy. Clin Cancer Res 17(6):1362–1372. https://doi.org/10.1158/1078-0432.CCR-10-2213

    Article  CAS  PubMed  Google Scholar 

  7. Guedan S, Rojas JJ, Gros A et al (2010) Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor growth. Mol Ther 18(7):1275–1283. https://doi.org/10.1038/mt.2010.79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. McKee TD, Grandi P, Mok W et al (2006) Degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector. Cancer Res 66(5):2509–2513. https://doi.org/10.1158/0008-5472.CAN-05-2242

    Article  CAS  PubMed  Google Scholar 

  9. Zhang W, Fulci G, Buhrman JS et al (2012) Bevacizumab with angiostatin-armed oHSV increases antiangiogenesis and decreases bevacizumab-induced invasion in U87 glioma. Mol Ther 20(1):37–45. https://doi.org/10.1038/mt.2011.187

    Article  CAS  PubMed  Google Scholar 

  10. Zhang W, Fulci G, Wakimoto H et al (2013) Combination of oncolytic herpes simplex viruses armed with angiostatin and IL-12 enhances antitumor efficacy in human glioblastoma models. Neoplasia 15(6):591–599

    Article  CAS  Google Scholar 

  11. Hardcastle J, Kurozumi K, Dmitrieva N et al (2010) Enhanced antitumor efficacy of vasculostatin (Vstat120) expressing oncolytic HSV-1. Mol Ther 18(2):285–294. https://doi.org/10.1038/mt.2009.232

    Article  CAS  PubMed  Google Scholar 

  12. Yoo JY, Haseley A, Bratasz A et al (2012) Antitumor efficacy of 34.5ENVE: a transcriptionally retargeted and "Vstat120"-expressing oncolytic virus. Mol Ther 20(2):287–297. https://doi.org/10.1038/mt.2011.208

    Article  CAS  PubMed  Google Scholar 

  13. Liu TC, Zhang T, Fukuhara H et al (2006) Dominant-negative fibroblast growth factor receptor expression enhances antitumoral potency of oncolytic herpes simplex virus in neural tumors. Clin Cancer Res 12(22):6791–6799. https://doi.org/10.1158/1078-0432.CCR-06-0263

    Article  CAS  PubMed  Google Scholar 

  14. Liu TC, Zhang T, Fukuhara H et al (2006) Oncolytic HSV armed with platelet factor 4, an antiangiogenic agent, shows enhanced efficacy. Mol Ther 14(6):789–797. https://doi.org/10.1016/j.ymthe.2006.07.011

    Article  CAS  PubMed  Google Scholar 

  15. Cheema TA, Wakimoto H, Fecci PE et al (2013) Multifaceted oncolytic virus therapy for glioblastoma in an immunocompetent cancer stem cell model. Proc Natl Acad Sci U S A 110(29):12006–12011. https://doi.org/10.1073/pnas.1307935110

    Article  PubMed  PubMed Central  Google Scholar 

  16. Markert JM, Cody JJ, Parker JN et al (2012) Preclinical evaluation of a genetically engineered herpes simplex virus expressing interleukin-12. J Virol 86(9):5304–5313. https://doi.org/10.1128/JVI.06998-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Saha D, Martuza RL, Rabkin SD (2017) Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade. Cancer Cell 32(2):253–267 e255. https://doi.org/10.1016/j.ccell.2017.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Terada K, Wakimoto H, Tyminski E et al (2006) Development of a rapid method to generate multiple oncolytic HSV vectors and their in vivo evaluation using syngeneic mouse tumor models. Gene Ther 13(8):705–714. https://doi.org/10.1038/sj.gt.3302717

    Article  CAS  PubMed  Google Scholar 

  19. Andreansky S, He B, van Cott J et al (1998) Treatment of intracranial gliomas in immunocompetent mice using herpes simplex viruses that express murine interleukins. Gene Ther 5(1):121–130. https://doi.org/10.1038/sj.gt.3300550

    Article  CAS  PubMed  Google Scholar 

  20. Barnard Z, Wakimoto H, Zaupa C et al (2012) Expression of FMS-like tyrosine kinase 3 ligand by oncolytic herpes simplex virus type I prolongs survival in mice bearing established syngeneic intracranial malignant glioma. Neurosurgery 71(3):741–748.; discussion 748. https://doi.org/10.1227/NEU.0b013e318260fd73

    Article  PubMed  PubMed Central  Google Scholar 

  21. Tamura K, Mawaribuchi S, Yoshimoto S et al (2010) Tumor necrosis factor-related apoptosis-inducing ligand 1 (TRAIL1) enhances the transition of red blood cells from the larval to adult type during metamorphosis in Xenopus. Blood 115(4):850–859. https://doi.org/10.1182/blood-2009-04-218966

    Article  CAS  PubMed  Google Scholar 

  22. Jahan N, Lee JM, Shah K et al (2017) Therapeutic targeting of chemoresistant and recurrent glioblastoma stem cells with a proapoptotic variant of oncolytic herpes simplex virus. Int J Cancer 141(8):1671–1681. https://doi.org/10.1002/ijc.30811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chase M, Chung RY, Chiocca EA (1998) An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy. Nat Biotechnol 16(5):444–448. https://doi.org/10.1038/nbt0598-444

    Article  CAS  PubMed  Google Scholar 

  24. Tyminski E, Leroy S, Terada K et al (2005) Brain tumor oncolysis with replication-conditional herpes simplex virus type 1 expressing the prodrug-activating genes, CYP2B1 and secreted human intestinal carboxylesterase, in combination with cyclophosphamide and irinotecan. Cancer Res 65(15):6850–6857. https://doi.org/10.1158/0008-5472.CAN-05-0154

    Article  CAS  PubMed  Google Scholar 

  25. Guffey MB, Parker JN, Luckett WS Jr et al (2007) Engineered herpes simplex virus expressing bacterial cytosine deaminase for experimental therapy of brain tumors. Cancer Gene Ther 14(1):45–56. https://doi.org/10.1038/sj.cgt.7700978

    Article  CAS  PubMed  Google Scholar 

  26. Sgubin D, Wakimoto H, Kanai R et al (2012) Oncolytic herpes simplex virus counteracts the hypoxia-induced modulation of glioblastoma stem-like cells. Stem Cells Transl Med 1(4):322–332. https://doi.org/10.5966/sctm.2011-0035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroaki Wakimoto .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Kahramanian, A., Kuroda, T., Wakimoto, H. (2019). Construction of Oncolytic Herpes Simplex Virus with Therapeutic Genes of Interest. In: Manfredsson, F., Benskey, M. (eds) Viral Vectors for Gene Therapy. Methods in Molecular Biology, vol 1937. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9065-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9065-8_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9064-1

  • Online ISBN: 978-1-4939-9065-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics