DNA-scaffolded biomaterials enable modular and tunable control of cell-based cancer immunotherapies [article]

Xiao Huang, Jasper Z. Williams, Ryan Chang, Zhongbo Li, Eric Gai, David M. Patterson, Yu Wei, Wendell A. Lim, Tejal A. Desai
2019 bioRxiv   pre-print
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
more » ... pact 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.
doi:10.1101/587105 fatcat:oiod57almzggvmvkqfnvidxm3m