Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy

Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 23 vom: 18. Juni, Seite e1807359
1. Verfasser: Hickey, John W (VerfasserIn)
Weitere Verfasser: Dong, Yi, Chung, Jae Wook, Salathe, Sebastian F, Pruitt, Hawley C, Li, Xiaowei, Chang, Calvin, Fraser, Andrew K, Bessell, Catherine A, Ewald, Andrew J, Gerecht, Sharon, Mao, Hai-Quan, Schneck, Jonathan P
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article T cell stimulation adoptive T cell therapy artificial matrix extracellular matrix hydrogel immunotherapy mechanotransduction Cytokines Hydrogels mehr... Ligands Receptors, Antigen, T-Cell Hyaluronic Acid 9004-61-9
Beschreibung
Zusammenfassung:© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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
Beschreibung:Date Completed 22.10.2019
Date Revised 04.04.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201807359