Induced pluripotent stem cell-derived dendritic cells potentiate the efficacy of interleukin-12-expressing oncolytic HSV-1.

Oncolytic herpes simplex virus type 1 (HSV-1), including marketing-approved G47Δ, elicits antitumor immunity via facilitating antigen presentation during immune-mediated clearance of infected tumor cells. Dendritic cell (DC) therapy should therefore enhance oncolytic HSV-1 efficacy, but its clinical application is hindered by the need to generate autologous DCs. Induced pluripotent stem cell (iPSC) technologies offer a scalable and standardized source of DCs. Here, we investigate the therapeutic potential of combining iPSC-derived DCs (iPSDCs) with an interleukin-12-expressing oncolytic HSV-1, T-mfIL12. iPSDCs, generated from a murine embryonic fibroblast-derived iPSC line, possess characteristics and functions comparable to bone marrow-derived DCs (BMDCs), including costimulatory molecule expression, antigen uptake capacity, and the ability to stimulate CD8+ and CD4+ T cells isolated from ovalbumin-specific transgenic mice both in vitro and in vivo. In a syngeneic murine bladder cancer model, iPSDCs markedly enhanced the efficacy of intratumorally inoculated T-mfIL12, eliciting augmented immune responses including intratumoral T cell infiltration, tumor-responsive T cell activation, and in situ maturation of DCs, similarly to BMDCs. The results indicate that iPSDCs can serve as an effective and practical alternative to conventional DCs in oncolytic virus immunotherapy. The combination of T-mfIL12 with iPSDCs offers a promising and clinically applicable cancer treatment strategy.