Cox Kevin M, Sterling Jason D, Regan Jeffrey T, Gasdaska John R, Frantz Karen K, Peele Charles G, Black Amelia, Passmore David, Moldovan-Loomis Cristina, Srinivasan Mohan, Cuison Severino, Cardarelli Pina M, Dickey Lynn F
Biolex Therapeutics, 158 Credle Street, Pittsboro, North Carolina 27312, USA.
Nat Biotechnol. 2006 Dec;24(12):1591-7. doi: 10.1038/nbt1260. Epub 2006 Nov 26.
N-glycosylation is critical to the function of monoclonal antibodies (mAbs) and distinguishes various systems used for their production. We expressed human mAbs in the small aquatic plant Lemna minor, which offers several advantages for manufacturing therapeutic proteins free of zoonotic pathogens. Glycosylation of a mAb against human CD30 was optimized by co-expressing the heavy and light chains of the mAb with an RNA interference construct targeting expression of the endogenous alpha-1,3-fucosyltransferase and beta-1,2-xylosyltransferase genes. The resultant mAbs contained a single major N-glycan species without detectable plant-specific N-glycans and had better antibody-dependent cell-mediated cytotoxicity and effector cell receptor binding activities than mAbs expressed in cultured Chinese hamster ovary (CHO) cells.
N-糖基化对单克隆抗体（mAb）的功能至关重要，并区分了用于生产它们的各种系统。我们在小型水生植物浮萍中表达了人源单克隆抗体，浮萍为生产无动物源性病原体的治疗性蛋白质提供了几个优势。通过将抗人CD30单克隆抗体的重链和轻链与靶向内源性α-1,3-岩藻糖基转移酶和β-1,2-木糖基转移酶基因表达的RNA干扰构建体共表达，优化了该单克隆抗体的糖基化。所得单克隆抗体含有单一主要N-聚糖种类，未检测到植物特异性N-聚糖，并且比在培养的中国仓鼠卵巢（CHO）细胞中表达的单克隆抗体具有更好的抗体依赖性细胞介导的细胞毒性和效应细胞受体结合活性。
