Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5522000 | Journal of Immunological Methods | 2017 | 9 Pages |
BackgroundAn 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.AimThis study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans.MethodsThree different doses (2, 8 or 16Â mg/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.ResultsAn 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 CD4Â +Â CD25Â + and CD8Â +Â CD25Â + subset of suppressor lymphocytes. A marked increase in CD4Â +Â CD25Â +Â FoxP3 regulatory T cells was noted in the 8Â mg treated group. In addition, NKT regulatory cells, CD3Â +Â CD69Â + and CD4Â +Â CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed.ConclusionAn 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.