Journal article
DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation
Nature nanotechnology, v 16(2), pp 214-223
01 Feb 2021
PMID: 33318641
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation
- Creators
- Xiao Huang - University of California, San FranciscoJasper Z Williams - University of California, San FranciscoRyan Chang - University of California, San FranciscoZhongbo Li - University of California, San FranciscoCassandra E Burnett - University of California, San FranciscoRogelio Hernandez-Lopez - University of California, San FranciscoInitha Setiady - University of California, San FranciscoEric Gai - University of California, San FranciscoDavid M Patterson - University of California, San FranciscoWei Yu - University of California, San FranciscoKole T Roybal - University of California, San FranciscoWendell A Lim - University of California, San FranciscoTejal A Desai (Corresponding Author) - University of California, San Francisco
- Publication Details
- Nature nanotechnology, v 16(2), pp 214-223
- Publisher
- Nature Publishing Group
- Grant note
- T32 GM007618 / NIGMS NIH HHS U54 CA244438 / NCI NIH HHS T32 GM008155 / NIGMS NIH HHS T32 AI007334 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000598709600002
- Scopus ID
- 2-s2.0-85100775192
- Other Identifier
- 991022130762904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Materials Science, Multidisciplinary
- Nanoscience & Nanotechnology