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DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation
Journal article   Peer reviewed

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

Xiao Huang, Jasper Z Williams, Ryan Chang, Zhongbo Li, Cassandra E Burnett, Rogelio Hernandez-Lopez, Initha Setiady, Eric Gai, David M Patterson, Wei Yu, …
Nature nanotechnology, v 16(2), pp 214-223
01 Feb 2021
PMID: 33318641
url
https://www.ncbi.nlm.nih.gov/pmc/articles/7878327View
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Abstract

Animals Antigen Presentation Biocompatible Materials - chemistry Biocompatible Materials - therapeutic use Cell Line, Tumor DNA - chemistry Humans Immunotherapy, Adoptive Lymphocyte Activation Mice Nanoparticles - chemistry Neoplasms - therapy Proteins - chemistry Proteins - immunology Proteins - therapeutic use Receptors, Chimeric Antigen - immunology T-Lymphocytes - immunology T-Lymphocytes - transplantation
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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Web of Science research areas
Materials Science, Multidisciplinary
Nanoscience & Nanotechnology
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