Resetting the autoreactive immune system with a therapeutic peptide in lupus

Over the last decade there has been a rapid expansion in the use of peptides as drugs. Nowadays, they are being used therapeutically in such diverse areas as endocrinology, neurology, haematology and some types of allergies. In the field of autoimmunity, a few candidates have emerged. Thus, in the pipeline of novel strategies designed to treat patients with systemic lupus erythematosus, the 21-mer peptide P140/Lupuzor raises hopes for the generation of an efficient, specific and safe treatment. This phosphopeptide has successfully completed a phase IIb clinical trial and will enter into a multi-centre, double-blind, placebo-controlled phase III clinical trial. The phase IIb trial showed that after three months of therapy (three subcutaneous injections of 200 µg peptide/patient in addition to standard of care), Lupuzor improved Systemic Lupus Erythematosus Disease Activity Index score of lupus patients under active treatment by 67.6% versus 41.5% in the placebo group (p < 0.025). After three additional months of follow-up, the improvement rate was 84.2% versus 45.8% (p < 0.025). The side-effect profile was unproblematic and the drug was well tolerated as evidenced by a very low drop-out rate. P140 does not behave as an immunosuppressant, it acts primarily as a fine immunomodulator of autoreactive CD4(+) T cells. Its underlying mechanism of action involves autophagy, a cellular process that implicates lysosomal-dependent recycling of intracellular components and controls the pool of major histocompatibility complex class II-displayed peptides that is presented to CD4(+) T cells.