A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis.
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.
Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: ilan@hadassah.org.il.
Yaron
Y
Ilan
Protalix Biotherapeutics, Israel.
Svetlana
S
Gingis-Velitski
Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Ami
A
Ben Ya'aco
Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Yehudit
Y
Shabbat
Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Lidya
L
Zolotarov
Protalix Biotherapeutics, Israel.
Einat
E
Almon
Protalix Biotherapeutics, Israel.
Yoseph
Y
Shaaltiel
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001706:Biopsy; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006505:Hepatitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D059828:Plant Cells; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha
Anti-TNF fusion protein; Colitis; Immune-mediated hepatitis; Oral tolerance