PT - JOURNAL ARTICLE AU - Xiao Huang AU - Jasper Z. Williams AU - Ryan Chang AU - Zhongbo Li AU - Eric Gai AU - David M. Patterson AU - Yu Wei AU - Wendell A. Lim AU - Tejal A. Desai TI - DNA-scaffolded biomaterials enable modular and tunable control of cell-based cancer immunotherapies AID - 10.1101/587105 DP - 2019 Jan 01 TA - bioRxiv PG - 587105 4099 - http://biorxiv.org/content/early/2019/03/23/587105.short 4100 - http://biorxiv.org/content/early/2019/03/23/587105.full AB - Advanced biomaterials provide versatile ways to spatially and temporally control immune cell activity, potentially enhancing their therapeutic potency and safety. Precise cell modulation demands multi-modal display of functional proteins with controlled densities on biomaterials. Here, we develop an artificial immune cell engager (AICE) platform – biodegradable particles onto which multiple proteins are densely loaded with ratiometric control via short nucleic acid tethers. We demonstrate the impact of AICE with varying ratios of anti-CD3 and anti-CD28 antibodies on ex vivo expansion of human primary T cells. We also show that AICE can be used to control the activity of engineered T cells in vivo. AICE injected intratumorally can provide a local priming signal for systemically administered AND-gate chimeric antigen receptor T cells, driving 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 over cell-based immunotherapies.