がん免疫サイクルをエンジニアリングされた二重標的ナノアダプターで近接・強化する

The cancer-immunity cycle (CIC) provides a conceptual framework for eliciting effective anti-tumor immune responses by targeting key events in systemic immunity. However, the successful completion of the CIC often requires the coordinated action of multiple therapeutic modalities, necessitating their integration into a unified system to overcome the limitations of conventional combination therapies. Here, we present a multimodal and programmable platform that integrates diverse therapeutic biomolecules into single agents, enabling the construction of versatile nanomedicines and bispecific antibodies through dual-targeted nano-adaptor (TNA) nanotechnology to potentiate the CIC. Specifically, TNA nanomedicines target five critical steps within the CIC, including antigen release, dendritic cell (DC) maturation, T-cell activation, mitigation of T-cell exhaustion, and tumor cell killing. Meanwhile, TNA bispecific antibodies enhance DC-T cell interactions to strengthen adaptive immunity and reinforce NK-tumor cell interactions to promote cytotoxicity. We demonstrate that TNAs elicit robust anti-tumor immunity, eradicating established tumors and suppressing metastatic dissemination. Owing to their modular and programmable architecture, TNAs hold broad potential for applications in immunotherapy and beyond.