Enhanced inhibition of syngeneic murine tumors by combinatorial therapy with genetically engineered HSV-1 expressing CCL2 and IL-12

Academic Article


  • Herpes simplex viruses type 1 (HSV-1) that lack the γ134.5 gene are unable to replicate in the central nervous system (CNS), but maintain replication competence in actively dividing tumors. To determine if antitumor therapy by M002, a γ134.5- HSV that expresses interleukin-12 (IL-12), could be augmented by combinatorial therapy with another γ134.5-deleted HSV-1 engineered to express the chemokine CCL2, Neuro-2a tumors were established subcutaneously in the syngeneic A/J mouse strain. Tumors received multiple injections intratumorally either of saline, the parent, non-cytokine-expressing virus R3659, M002, M010 (γ134. 5- HSV expressing CCL2), or a combination of M002 and M010. Efficacies were evaluated by monitoring inhibition of tumor growth over time. Results demonstrated the following: (1) inhibition of tumor growth was most pronounced in tumors treated with a combination of M002 and M010; (2) enhanced tumor growth inhibition for the combinatorial treatment group was statistically significant compared to either M002 or M010 alone; and (3) the variability between slopes of the tumor growth rates within an individual treatment group appeared to be virus-dependent, and was reproducible between experiments. Our results demonstrate that combinatorial cytokine/chemokine γ134. 5- HSV therapies can provide superior antitumor effects in experimental tumors as a model for malignancies arising in the brain. © 2005 Nature Publishing Group All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Parker JN; Meleth S; Hughes KB; Gillespie GY; Whitley RJ; Markert JM
  • Start Page

  • 359
  • End Page

  • 368
  • Volume

  • 12
  • Issue

  • 4