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Engineering an Artificial T‐Cell Stimulating Matrix for Immunotherapy
Author(s) -
Hickey John W.,
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 HaiQuan,
Schneck Jonathan P.
Publication year - 2019
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201807359
Subject(s) - cytotoxic t cell , extracellular matrix , microbiology and biotechnology , immunotherapy , t cell , cd8 , adoptive cell transfer , materials science , cancer immunotherapy , cancer research , immune system , biology , immunology , in vitro , biochemistry
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.