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CXCR4 Antagonist as an Adjuvant in Immunotherapy of Epithelial Ovarian Cancer

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Technical Report,15 Jun 2017,14 Jun 2018

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Health Research Inc., Roswell Park Comprehensive Cancer Center Buffalo United States

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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.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology
  • Biochemistry

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