Skip to main content
Journal cover image

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.

Publication ,  Journal Article
Barnard, Z; Wakimoto, H; Zaupa, C; Patel, AP; Klehm, J; Martuza, RL; Rabkin, SD; Curry, WT
Published in: Neurosurgery
September 2012

BACKGROUND: Glioblastoma is a fatal brain tumor in needing urgent effective therapy. Treatments with both oncolytic viruses and immunotherapy have shown preclinical efficacy and clinical promise. We sought to exploit possible synergies between oncolytic herpes simplex virus type 1 (oHSV-1) infection of intracranial gliomas and delivery of immune-stimulating fms-like tyrosine kinase 3 ligand (Flt3L) by engineering a herpes vector to express the cytokine. OBJECTIVE: To construct an oHSV-1 vector that expresses high levels of Flt3L and examine its antiglioma efficacy in an immunocompetent murine model. METHODS: G47Δ and a bacterial artificial chromosome system were used to generate a novel oHSV-1, termed G47Δ-Flt3L, expressing Flt3L. Cytokine expression was confirmed, and G47Δ-Flt3L was injected intratumorally into established intracranial CT-2A gliomas in syngeneic C57/Bl6 mice. Animals were followed for survival and assessed by the Kaplan-Meier method. RESULTS: G47Δ-Flt3L expressed high levels of Flt3L in culture. Expression of Flt3L affected neither viral replication nor had a cytotoxic effect on CT2A glioma cells. Direct inoculation into intracerebral CT2A glioma cells resulted in high levels of detectable Flt3L in mouse blood and was superior to parental G47Δ in prolonging survival in glioma-bearing animals. CONCLUSION: Treatment with G47Δ-Flt3L improves survival of glioma-bearing mice.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Neurosurgery

DOI

EISSN

1524-4040

Publication Date

September 2012

Volume

71

Issue

3

Start / End Page

741 / 748

Location

United States

Related Subject Headings

  • fms-Like Tyrosine Kinase 3
  • Transplantation, Isogeneic
  • Oncolytic Virotherapy
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Immunotherapy
  • Herpesvirus 1, Human
  • Glioma
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Barnard, Z., Wakimoto, H., Zaupa, C., Patel, A. P., Klehm, J., Martuza, R. L., … Curry, W. T. (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. https://doi.org/10.1227/NEU.0b013e318260fd73
Barnard, Zachary, Hiroaki Wakimoto, Cecile Zaupa, Anoop P. Patel, Jacquelyn Klehm, Robert L. Martuza, Samuel D. Rabkin, and William T. Curry. “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, no. 3 (September 2012): 741–48. https://doi.org/10.1227/NEU.0b013e318260fd73.
Barnard, Zachary, et al. “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, vol. 71, no. 3, Sept. 2012, pp. 741–48. Pubmed, doi:10.1227/NEU.0b013e318260fd73.
Barnard Z, Wakimoto H, Zaupa C, Patel AP, Klehm J, Martuza RL, Rabkin SD, Curry WT. 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. 2012 Sep;71(3):741–748.
Journal cover image

Published In

Neurosurgery

DOI

EISSN

1524-4040

Publication Date

September 2012

Volume

71

Issue

3

Start / End Page

741 / 748

Location

United States

Related Subject Headings

  • fms-Like Tyrosine Kinase 3
  • Transplantation, Isogeneic
  • Oncolytic Virotherapy
  • Neurology & Neurosurgery
  • Mice, Inbred C57BL
  • Mice
  • Immunotherapy
  • Herpesvirus 1, Human
  • Glioma
  • Disease Models, Animal