Cell Surface Engineering by Phase-Separated Coacervates for Antibody Display and Targeted Cancer Cell Therapy.

Autor: Chen H; Department of Chemistry and Center for Cell & Developmental Biology, The Chinese University of Hong Kong, Shatin, 99999, Hong Kong SAR, China., Bao Y; Department of Chemistry and Center for Cell & Developmental Biology, The Chinese University of Hong Kong, Shatin, 99999, Hong Kong SAR, China., Li X; Department of Chemistry and Center for Cell & Developmental Biology, The Chinese University of Hong Kong, Shatin, 99999, Hong Kong SAR, China., Chen F; Department of Physics, Hong Kong Baptist University, Kowloon Tong, 99999, Hong Kong SAR, China., Sugimura R; School of Biomedical Sciences, The University of Hong Kong, Hong Kong, 99999, Hong Kong SAR, China., Zeng X; Department of Physics, Hong Kong Baptist University, Kowloon Tong, 99999, Hong Kong SAR, China., Xia J; Department of Chemistry and Center for Cell & Developmental Biology, The Chinese University of Hong Kong, Shatin, 99999, Hong Kong SAR, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Oct 24; Vol. 63 (44), pp. e202410566. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1002/anie.202410566
Abstrakt: Cell therapies such as CAR-T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase-separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc-Lys-Gly-Dopa-OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe 3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody-embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody-dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer-targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy.
(© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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