CXCR4 Antagonist as an Adjuvant in Immunotherapy of Epithelial Ovarian Cancer
Abstract
We have analyzed the effect of a CXCR4 antagonist, expressed by oncolytic vaccinia virus or delivered in a soluble form by an intravenous or intraperitoneal injection, on metastatic dissemination of an invasive variant of the murine epithelial ovarian cancer cell line ID8-T. Using an orthotopic ID8-T tumor model in syngeneic mice, we have demonstrated that intraperitoneal delivery of a CXCR4 antagonist-expressing virus was more efficacious against ID8-T tumor than a systemic injection of the armed vector or soluble antagonists. The inhibition of tumor growth was dependent on the intratumoral concentration of the CXCR4 antagonist and virally-induced inflammation characterized by infiltration of CD8+ T cells and IL-12 cytokine-expressing tumor associated macrophages with concomitant inhibition of the immunosuppressive network. We conclude that targeting the CXCR4 signaling though intraperitoneally delivered oncolytic virotherapy together with the CXCR4 antagonist yields a significant therapeutic impact against metastatic ovarian cancer and may be included in multimodal virotherapy-based treatments in combination with cancer vaccines and adoptively-transferred T cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2017
- Accession Number
- AD1050206
Entities
People
- Danuta Kozbor