DataVXAdvanced SciencePaper
journal article·2025-04Open access

A CLDN18.2‐Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer

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

Advanced Science· Volume 12· Issue 16
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Source abstract

Abstract

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.
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Research context

Nanomaterials

OpenAlex topics: Cancer Immunotherapy and Biomarkers · Immune cells in cancer · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Gastrointestinal Cancer Translational Research Peking University Cancer Hospital & Institute Beijing 100142 China

CAS Key Laboratory of Molecular Imaging Institute of Automation Chinese Academy of Sciences Beijing 100190 China

University of Chinese Academy of Sciences Beijing 100080 China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Biochemistry and Molecular Biology Peking University Cancer Hospital & Institute Beijing 100142 China

School of Engineering Medicine & School of Biological Science and Medical Engineering Beihang University Beijing 100191 China

Key Laboratory of Big Data‐Based Precision Medicine (Beihang University) Ministry of Industry and Information Technology of China Beijing 100191 China

State 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 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Beijing Municipality

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