A flagellin-adjuvanted cancer vaccine combined with photodynamic therapy enhanced anti-tumor immune response in B16-F10 melanoma cancer model

Abstract

Abstract Immune checkpoint inhibitors have now become a standard therapy for malignant melanoma. However, immune checkpoint inhibitor monotherapy has shown effective in only a limited number of patients. Photodynamic (PDT) and immune combined therapy is a promising modality for the treatment of metastatic melanoma. Herein, we report the combination therapy with PDT and flagellin adjuvanted- Tyrp1/Trp2/gp100 peptides based vaccination (Fla-vax) in mouse models of B16-F10 melanoma cancer. We used the bilateral tumor model to determine whether the Fla-vax could induce systemic anti-tumor effects. The combination therapy with PDT and Fla-vax sufficiently induced systemic anti-tumor immune responses for local and abscopal tumor control,, with a significant increase in the systemic IFNγ/TNFα secretion from cytotoxic T lymphocytes (CTLs) and tumor-infiltrated effector memory CD8+ T cells. It was also found that the combined therapy greatly induced the number of migratory CD103+ DCs which is secreting CXCL10. The therapeutic benefit of PDT and Fla-vax proved to be CD8+ T-cell dependent, and the antitumor activity was additive with that provided by programmed death-1 (PD-1)-targeted immunotherapy. These results suggest the combination of active immunotherapy with tumor ablation by PDT as a feasible novel treatment strategy for advanced melanoma cancer.