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

Abstract 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.