A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis

作者：Ilan Yaron^*; Gingis Velitski Svetlana; Ben Ya'aco Ami; Shabbat Yehudit; Zolotarov Lidya; Almon Einat; Shaaltiel Yoseph

来源：Immunobiology, 2017, 222(3): 544-551.

DOI：10.1016/j.imbio.2016.11.001

• Anti-TNF fusion protein
• Oral tolerance
• Colitis
• Immune-mediated hepatitis

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.
Aim: To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106.
Methods: Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0.5 or 5 mu g 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.
Results: 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.
Conclusions: 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.

• 出版日期2017-3