Close and Enhance the Cancer‐Immunity Cycle by Engineered Dual‐Targeted Nano‐Adaptors
Abstract
ABSTRACT 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.
Article Details
Authors (13)
Pengkai Wu
Department of Hepatobiliary Surgery MOE Innovation Center for Basic Research in Tumor Immunotherapy Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
Ziqu Fang
Department of Hepatobiliary Surgery MOE Innovation Center for Basic Research in Tumor Immunotherapy Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
Longhui Wang
Department of Hepatobiliary Surgery MOE Innovation Center for Basic Research in Tumor Immunotherapy Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
Yong Zhu
Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering
Weiwei Long
Department of Hepatobiliary Surgery MOE Innovation Center for Basic Research in Tumor Immunotherapy Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
Mingshan Wang
Zhihao Sun
Rice Research Institute, Key Laboratory of Crop Molecular Improvement, Academy of Agricultural Sciences, Southwest University
Zulipikaer Wusiman
Department of Hepatobiliary Surgery MOE Innovation Center for Basic Research in Tumor Immunotherapy Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
Qiang Wang
Kaikai Wang
Dan Ding
Nanchang University , , ,
Dengqiu Xu
Department of Hepatobiliary Surgery MOE Innovation Center for Basic Research in Tumor Immunotherapy Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy The First Affiliated Hospital of Anhui Medical University Hefei Anhui China
Beicheng Sun