Antigen-Presenting Cell-Mimetic Scaffolds for ex vivo T Cell Expansion
Alexander S. Cheung1,2, David K. Zhang1,2, Sandeep T. Koshy1-3, and David J. Mooney1,2,*
1John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA; 2The Wyss Institute for Biologically Inspired Engineering Harvard University, Cambridge, Massachusetts, USA; 3Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA
Adoptive cell transfer (ACT) of T cells is a promising treatment for diverse malignancies. However, current approaches for ex vivo T cell expansion, a key step in ACT, frequently yield suboptimal expansion rates and limited functionality of cells. Here, high aspect ratio mesoporous silica micro-rods (MSRs) were coated with lipid to yield MSR-supported lipid bilayers (MSR-SLBs). MSR-SLBs locally presented cues for T cell receptor (TCR) stimulation and costimulation at predefined densities on a fluid lipid bilayer, and facilitated the controlled release of the soluble cue, interleukin-2, similar to how these cues are naturally presented by antigen-presenting cells (APCs). In cell culture, the material formed into a scaffold, creating an APC-mimetic microenvironment that promoted the efficient activation of infiltrating mouse and human T cells. MSR-SLBs promoted two- to ten-fold greater polyclonal T cell expansion than commercial expansion beads after two weeks. MSR-SLBs also promoted robust antigen-specific expansion of rare subpopulations of functional cytotoxic T cells from either T cell isolates, or peripheral blood mononuclear cells. This study demonstrates a new platform to rapidly expand functional T cells for ACT.
Funding for these studies was provided by the NIH (R01 EB015498)