Format:
Online-Ressource
ISSN:
2198-3844
Content:
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.
In:
day:17
In:
month:04
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year:2024
In:
extent:16
In:
Advanced science, Weinheim : Wiley-VCH, 2014-, (17.04.2024) (gesamt 16), 2198-3844
Language:
English
DOI:
10.1002/advs.202401100
URN:
urn:nbn:de:101:1-2404181418289.388406155941
URL:
https://doi.org/10.1002/advs.202401100
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2404181418289.388406155941
URL:
https://d-nb.info/1326615734/34
URL:
https://doi.org/10.1002/advs.202401100
