Alginate-based artificial antigen presenting cells expand functional CD8 T cells with memory characteristics for adoptive cell therapy.

Biomaterials

Department of Biomedical Engineering, School of Medicine, USA; Institute for Cell Engineering, School of Medicine, USA; Department of Pathology, School of Medicine, USA; Johns Hopkins Translational ImmunoEngineering Center, USA; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address:

Published: February 2025

The development of artificial Antigen Presenting Cells (aAPCs) has led to improvements in adoptive T cell therapy (ACT), an immunotherapy, for cancer treatment. aAPCs help to streamline the consistent production and expansion of T cells, thus reducing the time and costs associated with ACT. However, several issues still exist with ACT, such as insufficient T cell potency, which diminishes the translational potential for ACT. While aAPCs have been used primarily to increase production efficiency of T cells for ACT, the intrinsic properties of a biomaterial-based aAPC may affect T cell phenotype and function. In CD8 T cells, reactive oxygen species (ROS) and oxidative stress accumulation can activate Forkhead box protein O1 (FOXO1) to transcribe antioxidants which reduce ROS and improve memory formation. Alginate, a biocompatible and antioxidant rich biomaterial, is promising for incorporation into an aAPC formulation to modulate T cell phenotype. To investigate its utility, a novel alginate-based aAPC platform was developed that preferentially expanded CD8 T cells with memory related features. Alginate-based aAPCs allowed for greater control of CD8 T cell qualities, including, significantly improved in vivo persistence and augmented in vivo anti-tumor T cell responses.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423771PMC
http://dx.doi.org/10.1016/j.biomaterials.2024.122773DOI Listing

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