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DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation.

  • Author(s): Huang, Xiao
  • Williams, Jasper Z
  • Chang, Ryan
  • Li, Zhongbo
  • Burnett, Cassandra E
  • Hernandez-Lopez, Rogelio
  • Setiady, Initha
  • Gai, Eric
  • Patterson, David M
  • Yu, Wei
  • Roybal, Kole T
  • Lim, Wendell A
  • Desai, Tejal A
  • et al.

Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell-engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micrometre-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells. Locally retained ICEp presenting a high density of priming antigens activated CAR T cells, driving local tumour clearance while sparing uninjected tumours in immunodeficient mice. The ratiometric control of costimulatory ligands (anti-CD3 and anti-CD28 antibodies) and the surface presentation of a cytokine (IL-2) on ICEp were shown to substantially impact human primary T cell activation phenotypes. This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies.

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