CXCR4 Antagonist as an Adjuvant in Immunotherapy of Epithelial Ovarian Cancer
Technical Report,15 Jun 2017,14 Jun 2018
Health Research Inc., Roswell Park Comprehensive Cancer Center Buffalo United States
Pagination or Media Count:
Oncolytic viruses are capable of in situ vaccination as they induce immunogenic cell death in cancer cells and release tumor associated antigens for priming of tumor-specific CD8 T cells by tumor-infiltrating CD103 dendritic cells DCs. Using a metastatic ID8-T ovarian tumor model in syngeneic mice, we exploredwhether expansion of CD103 DCs following a CXCR4 antagonist-armed oncolytic vaccinia virus augments in situ booster immunization with a cancer peptide-based vaccine. We found that intratumoral delivery of the armed virus reduced tumor load and the immunosuppressive network leading to increased infiltration of CD8 T cells and phagocytic CD103 DCs at the tumor site. Expansion of the tumor-residing CD103 DC population by injection of the growth factor FLT3L into peritoneal cavities of ID8-T tumor bearing mice provided a platform for subsequent boost with a peptide-based adjuvanted vaccine that elicited potent CD8 T cell responses and inhibited tumor growth. Our results revealed that expansion of intratumoral CD103 DCs after CXCR4 antagonist-armed oncovirotherapy treatment enhanced in situ booster immunization with an adjuvanted tumor-specific peptide-based vaccine and improved therapeutic efficacy.
- Medicine and Medical Research