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

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.

Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy.

Helper (CD4+) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8+) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansion of antigen-specific CD4+ T cells hinders consistency and scalability of CD4+ T cell-based therapies, and complicates mechanistic studies. Here we describe a nanoparticle platform for ex vivo CD4+ T cell culture that mimics antigen presenting cells (APC) through display of major histocompatibility class II (MHC II) molecules. When combined with soluble co-stimulation signals, MHC II artificial APCs (aAPCs) expand cognate murine CD4+ T cells, including rare endogenous subsets, to induce potent effector functions in vitro and in vivo. Moreover, MHC II aAPCs provide help signals that enhance antitumor function of aAPC-activated CD8+ T cells in a mouse tumor model. Lastly, human leukocyte antigen class II-based aAPCs expand rare subsets of functional, antigen-specific human CD4+ T cells. Overall, MHC II aAPCs provide a promising approach for harnessing targeted CD4+ T cell responses.