Engineering M13 Filamentous Phages to Target Dendritic Cells and Elicit Anti-Tumour Immunity

Filamentous M13 phages are promising self-adjuvanting nanoparticles for cancer immunotherapy, but their efficacy remains limited by antigen versatility and immune targeting. Here, SCP is developed as an M13 phage-based vector that conjugates antigens via a SpyCatcher-SpyTag interface and presents dendritic cell (DC)-targeting peptides to enhance antigen uptake. SCP activates DCs in vitro, upregulating co-stimulatory markers and inflammatory gene signatures, which subsequently enhances T cell cytotoxicity. In vivo, SCP can be administered subcutaneously as a vaccine adjuvant or intratumourally as a therapy in multiple murine tumour models. SCP induces robust local inflammation, immunogenic cell death, and in situ tumour antigen release, driving tumour-specific cytotoxic T cell responses without requiring predefined neoantigens. Beyond promoting immune infiltration, SCP also reduces neovascularization, downregulates immune checkpoints, and elicits durable systemic immunity to prevent recurrence. Overall, SCP offers a scalable, cost-effective platform for enhancing tumour immunogenicity, bypassing the need for predefined neoantigen selection and exogenous vaccine production.