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

Abstract

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.