Purpose:Vaccinia virus (VV) has strong potential as a novel therapeutic agent for treatment of pancreatic cancer (PaCa). We investigated whether arming VV with IL10 could enhance the antitumor efficacy with the view that IL10 might dampen the host immunity to the virus, increasing viral persistence thus maximising the oncolytic effect and antitumor immunity associated with VV. Experimental Design:The antitumor efficacy of IL10-armed VV (VVL∆TK-IL10) and control VV∆TK was assessed in pancreatic cancer cell lines, mice bearing subcutaneous PaCa tumors and a PaCa transgenic mouse model. Viral persistence within the tumors was examined and immune depletion experiments as well as immunophenotyping of splenocytes were carried out to dissect the functional mechanisms associated with the viral efficacy. Results:Compared to unarmed VVL∆TK, VVL∆TK-IL10 had a similar level of cytotoxicity and replication in vitro in murine pancreatic cancer cell lines, but rendered a superior anti-tumor efficacy in the subcutaneous pancreatic cancer model and a K-ras-p53 mutant-transgenic PaCa model after systemic delivery, with induction of long-term antitumor immunity. The antitumor efficacy of the VV was dependent on CD4+ and CD8+, but not NK cells. Clearance of VVL∆TK-IL10 was reduced at early time points compared to the control virus. Treatment with VVL∆TK-IL10 resulted in a reduction in virus-specific, but not tumor-specific CD8+ cells compared to VVL∆TK. Conclusions:These results suggest that VVL∆TK-IL10 has strong potential as an antitumor therapeutic for PaCa.
- Received February 24, 2014.
- Revision received September 20, 2014.
- Accepted September 28, 2014.
- Copyright © 2014, American Association for Cancer Research.