Coating with flexible DNA network enhanced T-cell activation and tumor killing for adoptive cell the

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Adoptive cell therapy(ACT)is an emerging powerful cancer immunotherapy,which includes a complex process of genetic modification,stimulation and expansion.During these in vitro or ex vivo manipulation,sensitive cells are inescapability subjected to harmful external stimuli.Although a variety of cytoprotection strategies have been developed,their application on ACT remains challenging.Herein,a DNA network is constructed on cell surface by rolling circle amplification(RCA),and T cell-targeted trivalent tetrahedral DNA nanostructure is used as a rigid scaffold to achieve high-efficient and selective coating for T cells.The cytoprotective DNA network on T-cell surface makes them aggregate over time to form cell clusters,which exhibit more resistance to external stimuli and enhanced activities in human pe-ripheral blood mononuclear cells and liver cancer organoid killing model.Overall,this work provides a novel strategy for in vitro T cell-selective protection,which has a great potential for application in ACT.
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