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Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor
https://orcid.org/0000-0003-3529-5438
AbstractDue 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.
Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor
https://orcid.org/0000-0003-3529-5438
AbstractDue 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.
Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor
https://orcid.org/0000-0003-3529-5438
AbstractDue 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.
Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor
Advanced Science
Hao, Meixi (Autor:in) / Zhou, Ying (Autor:in) / Chen, Sijia (Autor:in) / Jin, Yu (Autor:in) / Li, Xiuqi (Autor:in) / Xue, Lingjing (Autor:in) / Shen, Mingxuan (Autor:in) / Li, Weishuo (Autor:in) / Zhang, Can (Autor:in)
Advanced Science ; 11
01.07.2024
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
Spatiotemporally Controlled T‐Cell Combination Therapy for Solid Tumor
| Wiley | 2024
| Wiley | 2025