CXCR4 Antagonist as an Adjuvant in Immunotherapy of Epithelial Ovarian Cancer
Abstract
The overall objective of this research project was to concomitantly reprogram the ovarian tumor microenvironment (TME) and tumor-specific T cell responses, while minimizing the potential for systemic toxicities. Because the CXCR4 receptor/CXCL12 chemokine signaling pathway triggers multiple adverse effects on ovarian cancer progression, we have developed a clinically translatable, oncolytic vaccinia virus expressing a CXCR4 antagonist (OVV-CXCR4-A) for reprograming the TME, and for sensitizing the tumor for treatment with dendritic cell (DC)vaccines and a novel adoptive T cell therapy. Using an orthotopic ID8-T ovarian tumor model in syngeneic mice,we 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. We also found that intratumoral delivery of the CXCR4-A-armed virus reduced tumor load and the immunosuppressive network in the TME, leading to increased efficacy of DC vaccines as well as infiltration of tumor antigen-specific CD8+ T cells due to upregulated pathways of T cell trafficking.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1123831
Entities
People
- Danuta Kozbor