文献类型：期刊文献

英文题名：A Spatially Controllable DNA Origami-Based T-Cell Cluster Engager for Precise Tumor Elimination

作者：Li, Hua-Dong[1,2,3];Shi, Wen-Jia[1];Xu, Jianjun[5];Li, Chao-Qiang[4];Liu, Yue[1];Zou, Tianhao[5];Li, Ying-Fu[1];Ma, Pei-Qiang[1];Ye, Bang-Ce[1];Yin, Bin-Cheng[1,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Biosyst & Microanal, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Renji Hosp, Inst Mol Med, Sch Med, Shanghai 200127, Peoples R China;[3]Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Key Lab Nucl Acid Chem & Nanomed, Shanghai 200127, Peoples R China;[4]Shihezi Univ, Sch Chem & Chem Engn, Shihezi 832000, Xinjiang, Peoples R China;[5]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Liver Transplant Ctr, Wuhan 430022, Hubei, Peoples R China

年份：2026

卷号：148

期号：2

起止页码：2758

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20260419949362);WOS:【SCI-EXPANDED(收录号:WOS:001656935800001)】；

基金：This work was jointly supported by the National Key Research and Development Program of China (Grant 2024YFA0917100), the National Natural Science Foundation of China (Grants 22374047, 22574051, 22134003, 22104037), the Natural Science Foundation of Shanghai (Grant 25ZR1403002), and the Fundamental Research Funds for the Central Universities. We thank the Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization experiments. We thank the staff members of the Integrated Laser Microscopy System/Molecular Imaging System at the National Facility for Protein Science in Shanghai (NFPS) (Shanghai Advanced Research Institute, Chinese Academy of Sciences) for AFM data collection and analysis.

语种：英文

外文关键词：Chemical activation - Cytotoxicity - DNA - Stability - T-cells

摘要：T cell-engaging therapy represents a cutting-edge approach in immuno-oncology that harnesses the power of the immune system to combat cancer. Despite its promise, challenges related to efficacy and safety limit its broader clinical application. Here we introduce SpTCE, a spatially controllable T-cell cluster engager based on DNA origami technology. SpTCE features an elegant two-layer architecture built on a DNA origami chassis. The inner functional layer is engineered to organize multiple, multivalent engaging antibodies and complementary hand-in-hand strands, which work together to enhance T-cell clustering and activation. The outer shielding layer integrates albumin binding domains with i-motif switches, which form a pH-responsive albumin coat and serve two functions: isolating the inner layer from healthy tissues and improving the structural stability of the DNA origami through an albumin coat. We validate acidic pH-triggered, specific T-cell cytotoxicity of SpTCE against tumor cells in vitro and observe the substantial intratumoral accumulation and improved physiological stability in vivo. As a proof of concept, we show that SpTCE effectively redirects T cells to eliminate tumors with high specificity and a more favorable off-tumor toxicity profile than a clinical-stage bispecific T cell engager. Collectively, these findings highlight the potential of SpTCE as a promising T-cell engager, offering precise control over T-cell activation while balancing efficacy and safety, and expanding the possibilities for advanced immuno-oncology treatments.