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HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer.

Publication ,  Journal Article
Benencia, F; Courrèges, MC; Conejo-García, JR; Mohamed-Hadley, A; Zhang, L; Buckanovich, RJ; Carroll, R; Fraser, N; Coukos, G
Published in: Mol Ther
November 2005

Cooperation between oncolytic herpes simplex virus (HSV) and host effector immune mechanisms has been previously described. In the present study, we investigated the mechanism underlying such cooperation in a murine syngeneic model of ovarian carcinoma. Therapeutic administration of HSV-1716, a replication-restricted mutant, resulted in significant reduction of tumor growth and a significant survival advantage. Intratumoral injection of HSV-1716 induced expression of IFN-gamma, MIG, and IP-10 in the tumor. This was accompanied by a significant increase in the number of tumor-associated NK and CD8+ T cells expressing CXCR3 and CD25. Ascites from HSV-1716-treated animals efficiently induced in vitro migration of NK and CD8+ T cells, which was dependent on the presence of MIG and IP-10. Murine monocytes and dendritic cells (DCs) were responsible for the production of MIG and IP-10 upon HSV-1716 infection. In monocytes, this was partially abrogated by neutralizing antibodies against IFN-alpha and -beta, thus indicating a role for type-1 IFNs in the reported effect. Human ovarian carcinomas showed high numbers of monocytes and DCs. Upon HSV-1716 infection, human monocyte-derived DCs produced large amounts of IFN-gamma and upregulated MIG and IP-10 expression. These results indicate that HSV-1716 induces an inflammatory response that may facilitate antitumor immune response upon oncolytic therapy.

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Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

November 2005

Volume

12

Issue

5

Start / End Page

789 / 802

Location

United States

Related Subject Headings

  • Up-Regulation
  • Simplexvirus
  • Receptors, Chemokine
  • Ovarian Neoplasms
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Activation
  • Interferons
  • Humans
  • Genetic Therapy
 

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Benencia, F., Courrèges, M. C., Conejo-García, J. R., Mohamed-Hadley, A., Zhang, L., Buckanovich, R. J., … Coukos, G. (2005). HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer. Mol Ther, 12(5), 789–802. https://doi.org/10.1016/j.ymthe.2005.03.026
Benencia, Fabian, Maria C. Courrèges, José R. Conejo-García, Alisha Mohamed-Hadley, Lin Zhang, Ronald J. Buckanovich, Richard Carroll, Nigel Fraser, and George Coukos. “HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer.Mol Ther 12, no. 5 (November 2005): 789–802. https://doi.org/10.1016/j.ymthe.2005.03.026.
Benencia F, Courrèges MC, Conejo-García JR, Mohamed-Hadley A, Zhang L, Buckanovich RJ, et al. HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer. Mol Ther. 2005 Nov;12(5):789–802.
Benencia, Fabian, et al. “HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer.Mol Ther, vol. 12, no. 5, Nov. 2005, pp. 789–802. Pubmed, doi:10.1016/j.ymthe.2005.03.026.
Benencia F, Courrèges MC, Conejo-García JR, Mohamed-Hadley A, Zhang L, Buckanovich RJ, Carroll R, Fraser N, Coukos G. HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer. Mol Ther. 2005 Nov;12(5):789–802.
Journal cover image

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

November 2005

Volume

12

Issue

5

Start / End Page

789 / 802

Location

United States

Related Subject Headings

  • Up-Regulation
  • Simplexvirus
  • Receptors, Chemokine
  • Ovarian Neoplasms
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Activation
  • Interferons
  • Humans
  • Genetic Therapy