title: An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase I clinical trial using a novel oral anti-TNF alpha-based therapy.
abstract: An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans.
  
  
  
  Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants. Subjects were followed for safety parameters and for an effect on T lymphocytes subsets and cytokine levels.
  
  
  
  An oral administration of PRX-106 was safe and well tolerated. The PK study showed that PRX106 is not absorbed. No effect on white blood cells and lymphocytes counts were noted. A dose dependent effect was noted on systemic lymphocytes. The oral administration of all three dosages was associated with an increase in CD4+CD25+ and CD8+CD25+ subset of suppressor lymphocytes. A marked increase in CD4+CD25+FoxP3 regulatory T cells was noted in the 8mg treated group. In addition, NKT regulatory cells, CD3+CD69+ and CD4+CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed.
  
  
  
  An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation. The PRX-106 may provide a safe orally administered effective anti-TNF alpha-based immune therapy for inflammatory bowel diseases and non-alcoholic steatohepatitis, as well as other autoimmune, TNF-mediated diseases.
authors.affiliation: Protalix Biotherapeutics, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Almon
authors.affiliation: Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Tawfik
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Drori
authors.affiliation: Protalix Biotherapeutics, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gingis-Velitski
authors.affiliation: Protalix Biotherapeutics, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Alon
authors.affiliation: Protalix Biotherapeutics, Israel.
authors.forename: Raul
authors.initials: R
authors.lastname: Chertkoff
authors.affiliation: Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Mushkat
authors.affiliation: Protalix Biotherapeutics, Israel.
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Shaaltiel
authors.affiliation: Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: ilan@hadassah.org.il.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000097:blood; D000068800:Etanercept / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept
keywords: Anti-TNF fusion protein; Oral tolerance