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231225s2019 xx |||||o 00| ||eng c |
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|a 10.1002/adma.201807359
|2 doi
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|a pubmed24n1364.xml
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|a (DE-627)NLM295898712
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|a (NLM)30968468
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Hickey, John W
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy
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|c 2019
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 22.10.2019
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|a Date Revised 04.04.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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|a T cell therapies require the removal and culture of T cells ex vivo to expand several thousand-fold. However, these cells often lose the phenotype and cytotoxic functionality for mediating effective therapeutic responses. The extracellular matrix (ECM) has been used to preserve and augment cell phenotype; however, it has not been applied to cellular immunotherapies. Here, a hyaluronic acid (HA)-based hydrogel is engineered to present the two stimulatory signals required for T-cell activation-termed an artificial T-cell stimulating matrix (aTM). It is found that biophysical properties of the aTM-stimulatory ligand density, stiffness, and ECM proteins-potentiate T cell signaling and skew phenotype of both murine and human T cells. Importantly, the combination of the ECM environment and mechanically sensitive TCR signaling from the aTM results in a rapid and robust expansion of rare, antigen-specific CD8+ T cells. Adoptive transfer of these tumor-specific cells significantly suppresses tumor growth and improves animal survival compared with T cells stimulated by traditional methods. Beyond immediate immunotherapeutic applications, demonstrating the environment influences the cellular therapeutic product delineates the importance of the ECM and provides a case study of how to engineer ECM-mimetic materials for therapeutic immune stimulation in the future
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|a Journal Article
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|a T cell stimulation
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|a adoptive T cell therapy
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|a artificial matrix
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|a extracellular matrix
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|a hydrogel
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|a immunotherapy
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4 |
|a mechanotransduction
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| 650 |
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|a Cytokines
|2 NLM
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| 650 |
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|a Hydrogels
|2 NLM
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| 650 |
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7 |
|a Ligands
|2 NLM
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| 650 |
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7 |
|a Receptors, Antigen, T-Cell
|2 NLM
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| 650 |
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|a Hyaluronic Acid
|2 NLM
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| 650 |
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7 |
|a 9004-61-9
|2 NLM
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| 700 |
1 |
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|a Dong, Yi
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chung, Jae Wook
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Salathe, Sebastian F
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Pruitt, Hawley C
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Li, Xiaowei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chang, Calvin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Fraser, Andrew K
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Bessell, Catherine A
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Ewald, Andrew J
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Gerecht, Sharon
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Mao, Hai-Quan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Schneck, Jonathan P
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 31(2019), 23 vom: 18. Juni, Seite e1807359
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnns
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| 773 |
1 |
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|g volume:31
|g year:2019
|g number:23
|g day:18
|g month:06
|g pages:e1807359
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| 856 |
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|u http://dx.doi.org/10.1002/adma.201807359
|3 Volltext
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