A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer
Abstract Precision treatment of gastric cancer requires specific biomarkers, and CLDN18.2 emerges as a promising target for patients’ stratification and therapeutic guidance. In 563 cases, 54.4% of patients are identified as CLDN18.2‐positive, with CLDN18.2 expression negatively correlated with immu...
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202413913 |
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| author | Xueying Wang Hui Hui Jing Han Ting Guo Yiding Wang Lin Meng Cong Chen Jie He Xiaoyong Guo Fuyu Zhong Hong Du Jie Tian Xiaofang Xing Yang Du Jiafu Ji |
| author_facet | Xueying Wang Hui Hui Jing Han Ting Guo Yiding Wang Lin Meng Cong Chen Jie He Xiaoyong Guo Fuyu Zhong Hong Du Jie Tian Xiaofang Xing Yang Du Jiafu Ji |
| author_sort | Xueying Wang |
| collection | DOAJ |
| description | Abstract Precision treatment of gastric cancer requires specific biomarkers, and CLDN18.2 emerges as a promising target for patients’ stratification and therapeutic guidance. In 563 cases, 54.4% of patients are identified as CLDN18.2‐positive, with CLDN18.2 expression negatively correlated with immune‐related factors like PD‐L1, indicating a “cold” tumor microenvironment. Here, a novel CLDN18.2 monoclonal antibody 1D5 is created with superior high specificity and affinity, and the antibody‐dependent fluorescence‐magnetic nanoparticle is developed for specific detection and magnetic hyperthermia (MHT). Under the assistance of sensitive fluorescence and deep‐penetrating magnetic particle imaging for tracing and timing the optimal nanoparticle dosage, MHT induces robust immunogenic response via DNA mismatch repair and tumor‐associated antigen release. It recruits CD11c+ dendritic cells, compensates PD‐1 in CD8+ T cells, and enhances CD86+ macrophage polarization. The combination of anti‐PD‐1 therapy increased TNF‐α and IFN‐γ secretion and further boosted the cytotoxic efficacy of CD8+ T cells. Excellent therapeutic efficacy is found simultaneously on cell‐derived allografts and patient‐derived xenografts based on this spatiotemporally manipulated strategy, presenting a therapeutic option for enhancing responsiveness to immunotherapy for CLDN18.2‐positive individuals. |
| format | Article |
| id | doaj-art-2eadde1f0fc349f69b7a254b78eea14b |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-2eadde1f0fc349f69b7a254b78eea14b2025-08-20T02:24:50ZengWileyAdvanced Science2198-38442025-04-011216n/an/a10.1002/advs.202413913A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric CancerXueying Wang0Hui Hui1Jing Han2Ting Guo3Yiding Wang4Lin Meng5Cong Chen6Jie He7Xiaoyong Guo8Fuyu Zhong9Hong Du10Jie Tian11Xiaofang Xing12Yang Du13Jiafu Ji14Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaCAS Key Laboratory of Molecular Imaging Institute of Automation Chinese Academy of Sciences Beijing 100190 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Biochemistry and Molecular Biology Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 ChinaSchool of Engineering Medicine & School of Biological Science and Medical Engineering Beihang University Beijing 100191 ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Gastrointestinal Cancer Centre Peking University Cancer Hospital & Institute Beijing 100142 ChinaCAS Key Laboratory of Molecular Imaging Institute of Automation Chinese Academy of Sciences Beijing 100190 ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Gastrointestinal Cancer Centre Peking University Cancer Hospital & Institute Beijing 100142 ChinaAbstract Precision treatment of gastric cancer requires specific biomarkers, and CLDN18.2 emerges as a promising target for patients’ stratification and therapeutic guidance. In 563 cases, 54.4% of patients are identified as CLDN18.2‐positive, with CLDN18.2 expression negatively correlated with immune‐related factors like PD‐L1, indicating a “cold” tumor microenvironment. Here, a novel CLDN18.2 monoclonal antibody 1D5 is created with superior high specificity and affinity, and the antibody‐dependent fluorescence‐magnetic nanoparticle is developed for specific detection and magnetic hyperthermia (MHT). Under the assistance of sensitive fluorescence and deep‐penetrating magnetic particle imaging for tracing and timing the optimal nanoparticle dosage, MHT induces robust immunogenic response via DNA mismatch repair and tumor‐associated antigen release. It recruits CD11c+ dendritic cells, compensates PD‐1 in CD8+ T cells, and enhances CD86+ macrophage polarization. The combination of anti‐PD‐1 therapy increased TNF‐α and IFN‐γ secretion and further boosted the cytotoxic efficacy of CD8+ T cells. Excellent therapeutic efficacy is found simultaneously on cell‐derived allografts and patient‐derived xenografts based on this spatiotemporally manipulated strategy, presenting a therapeutic option for enhancing responsiveness to immunotherapy for CLDN18.2‐positive individuals.https://doi.org/10.1002/advs.202413913CLDN18.2gastric cancerimmunotherapymagnetic hyperthermiamolecular imagingnanoparticle |
| spellingShingle | Xueying Wang Hui Hui Jing Han Ting Guo Yiding Wang Lin Meng Cong Chen Jie He Xiaoyong Guo Fuyu Zhong Hong Du Jie Tian Xiaofang Xing Yang Du Jiafu Ji A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer Advanced Science CLDN18.2 gastric cancer immunotherapy magnetic hyperthermia molecular imaging nanoparticle |
| title | A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer |
| title_full | A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer |
| title_fullStr | A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer |
| title_full_unstemmed | A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer |
| title_short | A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer |
| title_sort | cldn18 2 targeted nanoplatform manipulates magnetic hyperthermia spatiotemporally for synergistic immunotherapy in gastric cancer |
| topic | CLDN18.2 gastric cancer immunotherapy magnetic hyperthermia molecular imaging nanoparticle |
| url | https://doi.org/10.1002/advs.202413913 |
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