Cell surface engineering by phase-separated coacervates for antibody display and targeted cancer cell therapy

Tripeptide forms phase-separated coacervates, which functionalize the surface of NK cells, present an anti-HER2 mAb in the coacervate layer on the cell surface, and guide the NK cells to recognize and kill HER2+ cancer cells.

Abstract

Cell therapies such as CAR−T have demonstrated significant clinical success and have stimulated research into 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, which reflect the phase separation properties of ECM proteins, coat the surface of the natural killer (NK) cell using Fe³⁺ ions and create an outer layer that can encapsulate monoclonal antibodies (mAb) such as Trastuzumab. The antibody-embedded coacervate layer provides the NK cells with the ability to recognize and eliminate cancer cells through enhanced antibody-dependent cellular cytotoxicity (ADCC). Thus, this work 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.