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

Xiao Huang; Jasper Z. Williams; Ryan Chang; Zhongbo Li; Eric Gai; David M. Patterson; Yu Wei; Wendell A. Lim; Tejal A. Desai

In this work, we demonstrate a unique platform using synthetic short DNA oligonucleotides as surface scaffolds on biodegradable materials for the precise and controlled loading of multiple biomolecules at specific ratio and density. These advanced biomaterials possess the ability to regulate immune cells in the context of ex vivo and in vivo activation of both natural and engineered T cells. Through this highly modular platform, biocompatible materials can be employed as substrates for a wide spectrum of modulatory biomolecules, including cytokines 5 , antigens 10 , checkpoint inhibitors 43 , agonistic or antagonistic antibodies 44 , adjuvants 9, 11 , etc., to regulate the local environment and enhance the efficacy of immune cells in cancer immunotherapy 8 . Synthetic materials with tunable properties can enhance the pharmacokinetics of regulatory biomolecules in vivo 1, 6, 8 , and sometimes provide a necessary surface substrate for biomolecules to activate the cognate cell signaling 10, 25, 28 . Biomaterials fabricated with controlled size, shape, and composition -for example, microspheres, nanowires, and porous scaffolds -can also serve as a local adjuvant 2, 3, All rights reserved. No reuse allowed without permission.