Anti-viral Immunity in the Tumor Microenvironment: Implications for the Rational Design of Herpes Simplex Virus Type 1 Oncolytic Virotherapy

  • Paul J. F. RiderEmail author
  • Ifeanyi K. Uche
  • Larissa Sweeny
  • Konstantin G. Kousoulas
Microbial Anti-cancer Therapy and Prevention (PJF RIDER, L Sweeny AND KG KOUSOULAS, SECTION EDITORS)
Part of the following topical collections:
  1. Topical Collection on Microbial Anti-cancer Therapy and Prevention


Purpose of Review

The design of novel herpes simplex type I (HSV-1)–derived oncolytic virotherapies is a balancing act between safety, immunogenicity, and replicative potential. We have undertaken this review to better understand how these considerations can be incorporated into rational approaches to the design of novel herpesvirus oncolytic virotherapies.

Recent Findings

Several recent papers have demonstrated that enhancing the potential of HSV-1 oncolytic viruses to combat anti-viral mechanisms present in the tumor microenvironment leads to greater efficacy than their parental viruses.


It is not entirely clear how the immunosuppressive tumor microenvironment affects oncolytic viral replication and spread within tumors. Recent work has shown that the manipulation of specific cellular and molecular mechanisms of immunosuppression operating within the tumor microenvironment can enhance the efficacy of oncolytic virotherapy. We anticipate that future work will integrate greater knowledge of immunosuppression in tumor microenvironments with design of oncolytic virotherapies.


HSV Oncolytic Herpesvirus VC2 



We thank Dr. Rhonda Cardin and Dr. Rafiq Nabi for the helpful discussions in the preparation of this manuscript. This work was supported by the Louisiana Board of Regents Governor’s Biotechnology grant to K.G.K and Core Facilities supported by NIH:GM103424 and NIH GM110760. PJFR is funded by a National Institutes of Health COBRE grant (P20 GM121288).

Compliance with Ethical Standards

Conflict of Interest

Dr. Kousoulas reports non-financial support from Ios Biomedical Group, Inc. (IBG), outside the submitted work; in addition, Dr. Kousoulas has a patent “vaccines against genital herpes infections” (Patent number: 10130703) licensed to Ios Biomedical Group, Inc., and a patent “synthetic herpes simplex viruses type-1 for treatment of cancers” (Patent number: 8586028) issued.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science. 1991;252(5007):854–6.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Coen DM, Kosz-Vnenchak M, Jacobson JG, Leib DA, Bogard CL, Schaffer PA, et al. Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci U S A. 1989;86(12):4736–40.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ma W, He H, Wang H. Oncolytic herpes simplex virus and immunotherapy. BMC Immunol. 2018;19(1):40.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bommareddy PK, Patel A, Hossain S, Kaufman HL. Talimogene Laherparepvec (T-VEC) and other oncolytic viruses for the treatment of melanoma. Am J Clin Dermatol. 2017;18(1):1–15.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Harrington K, Freeman DJ, Kelly B, Harper J, Soria JC. Optimizing oncolytic virotherapy in cancer treatment. Nat Rev Drug Discov. 2019;18(9):689–706.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Shae D, Baljon JJ, Wehbe M, Becker KW, Sheehy TL, Wilson JT. At the bench: engineering the next generation of cancer vaccines. J Leukoc Biol. 2019.Google Scholar
  7. 7.
    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 Ther. 2003;10(4):292–303.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    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(4985):1262–6.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    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 U S A. 1992;89(8):3266–70.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Wilcox DR, Longnecker R. The Herpes Simplex Virus Neurovirulence Factor gamma34.5: revealing Virus-Host Interactions. PLoS Pathog. 2016;12(3):e1005449.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    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 U S A. 1997;94(3):843–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Verpooten D, Ma Y, Hou S, Yan Z, He B. Control of TANK-binding kinase 1-mediated signaling by the gamma(1)34.5 protein of herpes simplex virus 1. J Biol Chem. 2009;284(2):1097–105.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Yordy B, Iijima N, Huttner A, Leib D, Iwasaki A. A neuron-specific role for autophagy in antiviral defense against herpes simplex virus. Cell Host Microbe. 2012;12(3):334–45.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Trgovcich J, Johnson D, Roizman B. Cell surface major histocompatibility complex class II proteins are regulated by the products of the gamma(1)34.5 and U(L)41 genes of herpes simplex virus 1. J Virol. 2002;76(14):6974–86.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kanai R, Zaupa C, Sgubin D, Antoszczyk SJ, Martuza RL, Wakimoto H, et al. Effect of gamma34.5 deletions on oncolytic herpes simplex virus activity in brain tumors. J Virol. 2012;86(8):4420–31.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    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(6530):411–5.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Goldsmith K, Chen W, Johnson DC, Hendricks RL. Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. J Exp Med. 1998;187(3):341–8.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Mohr I, Sternberg D, Ward S, Leib D, Mulvey M, Gluzman Y. A herpes simplex virus type 1 gamma34.5 second-site suppressor mutant that exhibits enhanced growth in cultured glioblastoma cells is severely attenuated in animals. J Virol. 2001;75(11):5189–96.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Mulvey M, Camarena V, Mohr I. Full resistance of herpes simplex virus type 1-infected primary human cells to alpha interferon requires both the Us11 and gamma(1)34.5 gene products. J Virol. 2004;78(18):10193–6.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Markert JM, Malick A, Coen DM, Martuza RL. Reduction and elimination of encephalitis in an experimental glioma therapy model with attenuated herpes simplex mutants that retain susceptibility to acyclovir. Neurosurgery. 1993;32(4):597–603.PubMedCrossRefGoogle Scholar
  21. 21.
    Menotti L, Avitabile E, Gatta V, Malatesta P, Petrovic B, Campadelli-Fiume G. HSV as a platform for the generation of retargeted, armed, and reporter-expressing oncolytic viruses. Viruses. 2018;10(7).PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Goins WF, Hall B, Cohen JB, Glorioso JC. Retargeting of herpes simplex virus (HSV) vectors. Curr Opin Virol. 2016;21:93–101.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Zhou G, Roizman B. Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13alpha2 receptor. Proc Natl Acad Sci U S A. 2006;103(14):5508–13.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Mazzacurati L, Marzulli M, Reinhart B, Miyagawa Y, Uchida H, Goins WF, et al. Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV. Mol Ther. 2015;23(1):99–107.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Marzulli M, Mazzacurati L, Zhang M, Goins WF, Hatley ME, Glorioso JC, et al. A novel oncolytic herpes simplex virus design based on the common overexpression of microRNA-21 in tumors. J Gene Ther. 2018;3(1).Google Scholar
  26. 26.
    Lee CY, Bu LX, DeBenedetti A, Williams BJ, Rennie PS, Jia WW. Transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1 for targeting prostate tumors. Mol Ther. 2010;18(5):929–35.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Campbell SA, Mulvey M, Mohr I, Gromeier M. Attenuation of herpes simplex virus neurovirulence with picornavirus cis-acting genetic elements. J Virol. 2007;81(2):791–9.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Roizman B, Knipe D, Whitley RJ. Herpes simplex viruses. In: David M, Knipe PH, editors. Fields virology. 5th ed: Lippincott Williams & Wilkins; 2006. p. 2501–602.Google Scholar
  29. 29.
    • Jambunathan N, Charles AS, Subramanian R, Saied AA, Naderi M, Rider P, et al. Deletion of a predicted beta-sheet domain within the amino terminus of herpes simplex virus glycoprotein K conserved among Alphaherpesviruses prevents virus entry into neuronal axons. J Virol. 2015;90(5):2230–9 This publication identifies mutations in the amino terminus of HSV-1 gK which prevent entry into neurons via axonal termini. PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Bernstein DI, Pullum DA, Cardin RD, Bravo FJ, Dixon DA, Kousoulas KG. The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the Guinea pig model of genital herpes. Vaccine. 2019;37(1):61–8.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Stanfield BA, Stahl J, Chouljenko VN, Subramanian R, Charles AS, Saied AA, et al. A single intramuscular vaccination of mice with the HSV-1 VC2 virus with mutations in the glycoprotein K and the membrane protein UL20 confers full protection against lethal intravaginal challenge with virulent HSV-1 and HSV-2 strains. PLoS One. 2014;9(10):e109890.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Saied AA, Chouljenko VN, Subramanian R, Kousoulas KG. A replication competent HSV-1(McKrae) with a mutation in the amino-terminus of glycoprotein K (gK) is unable to infect mouse trigeminal ganglia after cornea infection. Curr Eye Res. 2014;39(6):596–603.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    David AT, Saied A, Charles A, Subramanian R, Chouljenko VN, Kousoulas KG. A herpes simplex virus 1 (McKrae) mutant lacking the glycoprotein K gene is unable to infect via neuronal axons and egress from neuronal cell bodies. MBio. 2012;3(4):e00144–12.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    • Richards AL, Sollars PJ, Pitts JD, Stults AM, Heldwein EE, Pickard GE, et al. The pUL37 tegument protein guides alpha-herpesvirus retrograde axonal transport to promote neuroinvasion. PLoS Pathog. 2017;13(12):e1006741 This publication identifies mutation in HSV-1 UL37 which disrupt retrograde transport to the nucleus after viral entry into neurons. PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Wirsching HG, Zhang H, Szulzewsky F, Arora S, Grandi P, Cimino PJ, et al. Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma. JCI Insight. 2019;4(13).Google Scholar
  36. 36.
    • Xu B, Ma R, Russell L, Yoo JY, Han J, Cui H, et al. An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma. Nat Biotechnol. 2018; In this study the authors generate an “armed” virus capable of expressing a ligand for an inhibitory NK cell receptor in infected cells. This enhances efficacy of oncolytic virotherapy. Google Scholar
  37. 37.
    Watanabe D, Goshima F. Oncolytic Virotherapy by HSV. Adv Exp Med Biol. 2018;1045:63–84.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    de Graaf JF, de Vor L, Fouchier RAM, van den Hoogen BG. Armed oncolytic viruses: a kick-start for anti-tumor immunity. Cytokine Growth Factor Rev. 2018;41:28–39.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Marelli G, Howells A, Lemoine NR, Wang Y. Oncolytic viral therapy and the immune system: a double-edged sword against cancer. Front Immunol. 2018;9:866.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Loret S, Guay G, Lippe R. Comprehensive characterization of extracellular herpes simplex virus type 1 virions. J Virol. 2008;82(17):8605–18.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Brown SM, MacLean AR, Aitken JD, Harland J. ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro. J Gen Virol. 1994;75(Pt 12):3679–86.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    • Pourchet A, Fuhrmann SR, Pilones KA, Demaria S, Frey AB, Mulvey M, et al. CD8(+) T-cell immune evasion enables oncolytic virus immunotherapy. EBioMedicine. 2016;5:59–67 This study describes restoration of TAP inhibition by HSV as enhancing the efficacy of HSV-1 oncolytic virotherapy. PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Griffin BD, Verweij MC, Wiertz EJ. Herpesviruses and immunity: the art of evasion. Vet Microbiol. 2010;143(1):89–100.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Alvarez-Breckenridge CA, Yu J, Price R, Wojton J, Pradarelli J, Mao H, et al. NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nat Med. 2012;18(12):1827–34.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Bolyard C, Meisen WH, Banasavadi-Siddegowda Y, Hardcastle J, Yoo JY, Wohleb ES, et al. BAI1 orchestrates macrophage inflammatory response to HSV infection-implications for oncolytic viral therapy. Clin Cancer Res. 2017;23(7):1809–19.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Denton NL, Chen CY, Hutzen B, Currier MA, Scott T, Nartker B, et al. Myelolytic treatments enhance oncolytic herpes virotherapy in models of Ewing sarcoma by modulating the immune microenvironment. Mol Ther Oncolytics. 2018;11:62–74.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Koppers-Lalic D, Reits EA, Ressing ME, Lipinska AD, Abele R, Koch J, et al. Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing. Proc Natl Acad Sci U S A. 2005;102(14):5144–9.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Wei H, Wang Y, Chowdhury SI. Bovine herpesvirus type 1 (BHV-1) UL49.5 luminal domain residues 30 to 32 are critical for MHC-I down-regulation in virus-infected cells. PLoS One. 2011;6(10):e25742.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Chowdhury SI, Wei H, Weiss M, Pannhorst K, Paulsen DB. A triple gene mutant of BoHV-1 administered intranasally is significantly more efficacious than a BoHV-1 glycoprotein E-deleted virus against a virulent BoHV-1 challenge. Vaccine. 2014;32(39):4909–15.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Lampen MH, Verweij MC, Querido B, van der Burg SH, Wiertz EJ, van Hall T. CD8+ T cell responses against TAP-inhibited cells are readily detected in the human population. J Immunol. 2010;185(11):6508–17.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Oliveira CC, van Hall T. Alternative antigen processing for MHC class I: multiple roads lead to Rome. Front Immunol. 2015;6:298.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Rajaraman S, Canjuga D, Ghosh M, Codrea MC, Sieger R, Wedekink F, et al. Measles virus-based treatments trigger a pro-inflammatory cascade and a distinctive immunopeptidome in glioblastoma. Mol Ther Oncolytics. 2019;12:147–61.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Gulley JL, Madan RA, Pachynski R, Mulders P, Sheikh NA, Trager J, et al. Role of antigen spread and distinctive characteristics of immunotherapy in cancer treatment. J Natl Cancer Inst. 2017;109(4).Google Scholar
  54. 54.
    Looker KJ, Magaret AS, May MT, Turner KM, Vickerman P, Gottlieb SL, et al. Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS One. 2015;10(10):e0140765.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    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 Ther. 1999;6(10):1751–8.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Ito M, Maruyama T, Saito N, Koganei S, Yamamoto K, Matsumoto N. Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity. J Exp Med. 2006;203(2):289–95.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science. 1998;280(5369):1618–20.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Tachibana K, Nakanishi H, Mandai K, Ozaki K, Ikeda W, Yamamoto Y, et al. Two cell adhesion molecules, nectin and cadherin, interact through their cytoplasmic domain-associated proteins. J Cell Biol. 2000;150(5):1161–76.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Han J, Chen X, Chu J, Xu B, Meisen WH, Chen L, et al. TGFbeta treatment enhances glioblastoma virotherapy by inhibiting the innate immune response. Cancer Res. 2015;75(24):5273–82.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554(7693):538–43.PubMedCrossRefGoogle Scholar
  61. 61.
    Delwar ZM, Kuo Y, Wen YH, Rennie PS, Jia W. Oncolytic virotherapy blockade by microglia and macrophages requires STAT1/3. Cancer Res. 2018;78(3):718–30.PubMedCrossRefGoogle Scholar
  62. 62.
    Meisen WH, Wohleb ES, Jaime-Ramirez AC, Bolyard C, Yoo JY, Russell L, et al. The impact of macrophage- and microglia-secreted TNFalpha on oncolytic HSV-1 therapy in the glioblastoma tumor microenvironment. Clin Cancer Res. 2015;21(14):3274–85.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Thorne AH, Meisen WH, Russell L, Yoo JY, Bolyard CM, Lathia JD, et al. Role of cysteine-rich 61 protein (CCN1) in macrophage-mediated oncolytic herpes simplex virus clearance. Mol Ther. 2014;22(9):1678–87.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Lobel M, Bauer S, Meisel C, Eisenreich A, Kudernatsch R, Tank J, et al. CCN1: a novel inflammation-regulated biphasic immune cell migration modulator. Cell Mol Life Sci. 2012;69(18):3101–13.PubMedCrossRefGoogle Scholar
  65. 65.
    Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature. 2007;450(7168):430–4.PubMedCrossRefGoogle Scholar
  66. 66.
    Das S, Owen KA, Ly KT, Park D, Black SG, Wilson JM, et al. Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc Natl Acad Sci U S A. 2011;108(5):2136–41.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Denton NL, Chen CY, Scott TR, Cripe TP. Tumor-associated macrophages in oncolytic virotherapy: friend or foe? Biomedicines. 2016;4(3).PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Rydyznski C, Daniels KA, Karmele EP, Brooks TR, Mahl SE, Moran MT, et al. Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells. Nat Commun. 2015;6:6375.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Stanfield BA, Rider PJF, Caskey J, Del Piero F, Kousoulas KG. Intramuscular vaccination of guinea pigs with the live-attenuated human herpes simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and regulatory Tr1 responses. Vaccine. 2018;36(20):2842–9.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Bernstein DI, Cardin RD, Pullum DA, Bravo FJ, Kousoulas KG, Dixon DA. Duration of protection from live attenuated vs. sub unit HSV-2 vaccines in the guinea pig model of genital herpes: reassessing efficacy using endpoints from clinical trials. PLoS One. 2019;14(3):e0213401.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Kennedy EM, Farkaly T, Behera P, Colthart A, Goshert C, Jacques J, et al. Design of ONCR-177 base vector, a next generation oncolytic herpes simplex virus type-1, optimized for robust oncolysis, transgene expression and tumor-selective replication [abstract]. Proceedings of the American Association for Cancer Research Annual Meeting 2019. 2019 Mar 29-Apr 3;Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1455.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Paul J. F. Rider
    • 1
    Email author
  • Ifeanyi K. Uche
    • 1
  • Larissa Sweeny
    • 1
    • 2
  • Konstantin G. Kousoulas
    • 1
  1. 1.Division of Biotechnology and Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary MedicineLouisiana State UniversityBaton RougeUSA
  2. 2.Louisiana State University Health Sciences CenterNew OrleansUSA

Personalised recommendations