Department of Chemistry and Center for Cell & Developmental Biology, The Chinese University of Hong Kong, Shatin, 99999, Hong Kong SAR, China.
Department of Physics, Hong Kong Baptist University, Kowloon Tong, 99999, Hong Kong SAR, China.
Angew Chem Int Ed Engl. 2024 Oct 24;63(44):e202410566. doi: 10.1002/anie.202410566. Epub 2024 Sep 25.
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 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.
细胞疗法，如嵌合抗原受体 T 细胞（CAR-T）疗法，已经取得了显著的临床成功，这推动了使用天然和合成材料对免疫细胞表面工程的研究，以增强其治疗性能。然而，许多这些材料并不能完全复制细胞外基质（ECM）的动态性质。本研究提出了一种利用相分离肽凝聚物来修饰免疫细胞表面的细胞表面工程策略。我们精心设计了一种三肽，Fmoc-Lys-Gly-Dopa-OH（KGdelta；Fmoc=芴甲氧羰基；delta=Dopa，二羟苯丙氨酸），它在水溶液中通过相分离形成凝聚物。这些凝聚物模仿 ECM 蛋白的相分离特性，在 Fe 离子的辅助下将自然杀伤（NK）细胞表面包裹起来，并形成一个能够包封单克隆抗体（mAb）的外层，如曲妥珠单抗。抗体嵌入凝聚物层赋予 NK 细胞识别癌细胞并通过增强抗体依赖性细胞毒性（ADCC）消除它们的能力。这项工作因此提出了一种独特的细胞表面功能化策略，并展示了其在展示针对癌症的靶向 mAb 用于癌症治疗中的应用，突出了其在癌症治疗领域的潜在应用。
