Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor
Abstract: Due to multidimensional complexity of solid tumor, development of rational T‐cell combinations and corresponding formulations is still challenging. Herein, a triple combination of T cells are developed with Indoleamine 2,3‐dioxygenase inhibitors (IDOi) and Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i). To maximize synergism, a spatiotemporally controlled T‐cell engineering technology to formulate triple drugs into one cell therapeutic, is established. Specifically, a sequentially responsive core‐shell nanoparticle (SRN) encapsulating IDOi and CDK4/6i is anchored onto T cells. The yielded SRN‐T cells migrated into solid tumor, and achieved a 1st release of IDOi in acidic tumor microenvironment (TME). Released IDOi restored tryptophan supply in TME, which activated effector T cells and inhibited Tregs. Meanwhile, 1st released core is internalized by tumor cells and degraded by glutathione (GSH), to realize a 2nd release of CDK4/6i, which induced up‐regulated expression of C‐X‐C motif chemokine ligand 10 (CXCL10) and C‐C motif chemokine ligand 5 (CCL5), and thus significantly increased tumor infiltration of T cells. Together, with an enhanced recruitment and activation, T cells significantly suppressed tumor growth, and prolonged survival of tumor‐bearing mice. This study demonstrated rationality and superiority of a tri‐drug combination mediated by spatiotemporally controlled cell‐engineering technology, which provides a new treatment regimen for solid tumor.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor ; day:17 ; month:04 ; year:2024 ; extent:16
Advanced science ; (17.04.2024) (gesamt 16)
- Creator
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Hao, Meixi
Zhou, Ying
Chen, Sijia
Jin, Yu
Li, Xiuqi
Xue, Lingjing
Shen, Mingxuan
Li, Weishuo
Zhang, Can
- DOI
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10.1002/advs.202401100
- URN
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urn:nbn:de:101:1-2404181418289.388406155941
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
- 14.08.2025, 10:55 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Hao, Meixi
- Zhou, Ying
- Chen, Sijia
- Jin, Yu
- Li, Xiuqi
- Xue, Lingjing
- Shen, Mingxuan
- Li, Weishuo
- Zhang, Can
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