Ilan Yaron, Gingis-Velitski Svetlana, Ben Ya'aco Ami, Shabbat Yehudit, Zolotarov Lidya, Almon Einat, Shaaltiel Yoseph
Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Protalix Biotherapeutics, Israel.
Immunobiology. 2017 Mar;222(3):544-551. doi: 10.1016/j.imbio.2016.11.001. Epub 2016 Nov 4.
The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain.
To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106.
Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0.5 or 5μg PRX 106. In the colitis model, TNBS-colitis was induced in mice followed by the oral administration of plant cells expressing PRX-106. The immune modulatory effect was determined through follow-up to assess the clinical effect, histology, and serum cytokine levels and by FACS analysis for lymphocyte subsets.
The oral administration of BY-2 cells expressing PRX-106 alleviated immune-mediated liver injury. Serum AST and ALT levels decreased and were comparable to those of mice that had received high-dose steroids. The beneficial effect was also observed as a marked decrease in hepatic necrosis. In the colitis model, the oral administration of BY-2 plant cells expressing PRX-106 alleviated weight loss associated with immune-mediated colitis and improved bowel histology. A reduction in I-IkB-alpha phosphorylation in treated mice was also observed. These effects were associated with a significant alteration in the distribution of CD4+CD25+FOXP3+ cells.
Plant cells expressing recombinant anti-TNF fusion protein show biological activity when orally administered, exerting an immune modulatory effect through the alleviation of immune-mediated hepatitis and immune-mediated colitis.
口服的BY-2植物细胞表达的重组抗TNF融合蛋白（PRX-106）（n = 6）由与人抗体IgG1结构域的Fc成分融合的人TNF受体（TNFR）的可溶性形式组成。
评估口服表达PRX-106的植物细胞的免疫调节作用。
用伴刀豆球蛋白A（ConA）诱导免疫性肝炎的小鼠口服含0.5或5μg PRX 106的表达PRX-106的细胞。在结肠炎模型中，先诱导小鼠发生三硝基苯磺酸（TNBS）结肠炎，然后口服表达PRX-106的植物细胞。通过随访评估临床效果、组织学和血清细胞因子水平，并通过流式细胞术分析淋巴细胞亚群来确定免疫调节作用。
口服表达PRX-106的BY-2细胞可减轻免疫介导的肝损伤。血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平降低，与接受高剂量类固醇的小鼠相当。还观察到肝坏死明显减少的有益效果。在结肠炎模型中，口服表达PRX-106的BY-2植物细胞可减轻与免疫介导的结肠炎相关的体重减轻，并改善肠道组织学。还观察到治疗小鼠中I-κB-α磷酸化减少。这些作用与CD4 + CD25 + FOXP3 +细胞分布的显著改变有关。
表达重组抗TNF融合蛋白的植物细胞口服时具有生物活性，通过减轻免疫介导的肝炎和免疫介导的结肠炎发挥免疫调节作用。
