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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Benencia, F; Courrèges, MC; Conejo-García, JR; Mohamed-Hadley, A; Zhang, L; Buckanovich, RJ; Carroll, R; Fraser, N; Coukos, G

Published Date

  • November 2005

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 789 - 802

PubMed ID

  • 15925544

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1016/j.ymthe.2005.03.026


  • eng

Conference Location

  • United States