Abstract
Abstract Advanced biomaterials can be used to spatially and temporally control immune cell activities to improve the efficacy and safety of cell therapies. Precise immune cell modulation demands multi-modal display of functional proteins on biomaterials with a high level of control. Here, we developed biodegradable immune cell engaging particles (ICEp) with synthetic short DNA as scaffolds for efficient and tunable protein loading. We demonstrate the precise ratiometric control of anti-CD3 and anti-CD28 antibodies on this biodegradable platform can impact the quality of ex vivo expanded human primary T cells. Furthermore, the high-density presentation of antigens, difficult to achieve by other chemistries, is necessary for controlling the activity of engineered T cells in vivo. Antigen-presenting ICEp injected intratumorally can provide a local priming signal for systemically administered AND-gate chimeric antigen receptor (CAR) T cells that recognize dual antigens: the first antigen on ICEp activates CAR expression to target the second antigen on tumor cells. This leads to local tumor clearance while sparing uninjected tumors that model potentially cross-reactive healthy tissues. This modularly functionalized biomaterial thus provides a flexible platform to achieve sophisticated control of cell-based immunotherapies.
Published Version
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