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bioRxiv · 10.1101/587105

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

Huang, X.·Williams, J. Z.·Chang, R.·Li, Z.·Gai, E.·Patterson, D. M.·Yu, W.·Lim, W. A.·Desai, T. A.
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Abstract

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.

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Huang, X., Williams, J. Z., Chang, R., Li, Z., Gai, E., Patterson, D. M., Yu, W., Lim, W. A., Desai, T. A.. 2019-03-23. DNA-scaffolded biomaterials enable modular and tunable control of cell-based cancer immunotherapies. https://doi.org/10.1101/587105

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