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Screening T‑Cell Activity via a Photodetachable DNA-Copolymer Nanocage and Its Therapeutic Application

Screening T-cell activity and selecting active ones from large ex vivo-expanded populations before reinfusion is important for the success of T-cell therapy. Cytokine secretion is the evaluation criterion of cell immune activity. Cell membrane-anchored probes and microchamber-based techniques have b...

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Published in:Analytical chemistry (Washington) 2022-09, Vol.94 (38), p.13205-13214
Main Authors: Fang, Yanyun, Yan, Yawei, Bi, Shiyi, Wang, Yingfei, Chen, Yue, Xu, Peipei, Ju, Huangxian, Liu, Ying
Format: Article
Language:English
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Summary:Screening T-cell activity and selecting active ones from large ex vivo-expanded populations before reinfusion is important for the success of T-cell therapy. Cytokine secretion is the evaluation criterion of cell immune activity. Cell membrane-anchored probes and microchamber-based techniques have been used to screen cytokine secretion at the single-cell level. However, they are either easily affected by nearby cells’ secretion or lack of single-cell encapsulation efficiency. Here, we design a photodetachable DNA-copolymer nanocage on the cell membrane for screening the activities of ex vivo-expanded T cells by in-situ monitoring cytokine interferon-gamma (IFN-γ) secretion. The ones with good immune activity are selected for therapeutic application. DNA-copolymer nanocage is self-assembled on a cell membrane to encapsulate a single T cell. A self-quenched IFN-γ recognition aptamer is contained in the DNA-copolymer nanocage, which recovers fluorescence in response to IFN-γ secretion to indicate individual T-cell activity. The active T cells are collected after fluorescence-activated cell sorting, irradiated with 5 min UV light to detach nanocage from the cell membrane, and continuously cocultured with downstream cells. The selected Jurkat cells and CD19 CAR-T cells showed improved capabilities for downstream cell activation and cancer cell killing. The cell membrane-detachable DNA-copolymer nanocage-based T-cell activity screening and selection would have promising applications in T-cell therapy.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.2c02763