The therapeutic P140 peptide, a new immunomodulating tool for lupus may have applications in other chronic inflammatory conditions

Abstract

P140 is a synthetic peptide issued from the U1-70K protein. It was chemically modified and contains a phosphoserine residue at position 140. P140/Lupuzorâ had no adverse safety signals and met its primary efficacy end points in a multicenter, randomized, placebo-controlled phase IIb study for lupus. A phase III-clinical trial is currently on-going for this indication. The mechanism of action of P140 has been recently elucidated in MRL/lpr lupus-prone mice. P140 binds HSPA8/ HSC70 chaperone protein, decreases its expression and reduces autophagic flux in B-lymphocytes of peptide-treated MRL/ lpr mice. P140 interferes with a selective form of autophagy called chaperone-mediated autophagy or CMA. It induces a lower expression class II-MHC molecules and alters the presentation of peptides to autoreactive T cells, leading to a reduction T and B cells activation and a drop of potentially pathogenic autoantibodies.