Polymerised superparamagnetic antigen presenting cell lymphocyte capture for enriching tumour reactive T-cells and neoantigen identification

Chung-Yao Hsu, Po-Cheng Tsai, Jung-Chen Lin, Chen-Hsueh Pai, Yun-Jui Teng, Bing-Yu Yao, Cheng-Yin Fei, Gwo Harn Max Shiau, Leon CW Lin, Sean Lo, Hung-Chih Yang () and Che-Ming Jack Hu ()
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Chung-Yao Hsu: National Yang Ming Chao Tung University and Academia Sinica
Po-Cheng Tsai: National Yang Ming Chao Tung University and Academia Sinica
Jung-Chen Lin: Academia Sinica
Chen-Hsueh Pai: Academia Sinica
Yun-Jui Teng: National Taiwan University
Bing-Yu Yao: Academia Sinica
Cheng-Yin Fei: National Yang Ming Chao Tung University and Academia Sinica
Gwo Harn Max Shiau: Academia Sinica
Leon CW Lin: Academia Sinica
Sean Lo: Academia Sinica
Hung-Chih Yang: National Taiwan University
Che-Ming Jack Hu: National Yang Ming Chao Tung University and Academia Sinica

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Ultrasensitive antigen recognition between T lymphocytes and cognate targets via immunological synapse (IS) formation enables live cell-based antigen-specific T cell detection. However, unpredictable antigen processing and major histocompatibility complex (MHC) turnover limit specificity. Here, intracellularly polymerized antigen-presenting cells (pAPCs) are developed for modular, persistent antigen display via kinetically driven loading. Although inanimate, pAPCs mimic cellular interactions, inducing IS hallmarks such as supramolecular activation cluster formation, cytoskeletal contraction, and trogocytosis. Incorporation of superparamagnetic nanoparticles allows label-free magnetic isolation of antigen-specific T cells, surpassing MHC-conjugated beads in sensitivity and specificity. In tumor-bearing hosts, pAPCs enrich tumor-reactive lymphocytes, enhancing adoptive T cell therapy and neoantigen-specific T cell identification. Additionally, pAPCs from engineered cells expressing monovalent human MHC enrich virus- and tumor-specific CD8 T cells from human peripheral blood mononuclear cells and human leukocyte antigen-transgenic mice, demonstrating the potential of this cell–gel hybrid platform for precise antigen-specific T cell capture.

Date: 2025
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DOI: 10.1038/s41467-025-60321-3

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