Stress proteins or heat-shock proteins (HSP) play an important role in the regulation of the human immune system. They are up-regulated during inflammation and can therefore be considered as biomarkers of inflammation. Their main function is to protect cells from lethal damage under stressful circumstances such as inflammation.
Recent work in the group of Prof. Dr.. van Eden at Utrecht University has shown that administration of HSP70 and peptides derived from HSP proteins suppress disease in animal models of autoimmunity. This suppression could be transferred to untreated recipients and was found to be active both prophylactically and therapeutically.
Trajectum Pharma has an exclusive license to this patented technology. A lead compound, a small peptide consisting of 15 amino acids, has meanwhile been identified and formal development of this compound, designated B29, was initiated.
B29 exerts its pharmacological action through the activation and/or induction of regulatory T cells (Tregs), which are a specific T cell subset with immunosuppressive capacities.
Under natural circumstances, Treg induction occurs to protect the body from overreacting to e.g. infection.
In case of autoimmune diseases, the approach is to mimic this natural selfcontrolling system by actively immunizing with B29, which has been shown to induce regulatory T cells in vivo (van Herwijnen MJC et al. PNAS 2012, 109:14134-9). Such T cells are both prophylactically and therapeutically active. As physiological (natural) mechanisms of immunity are involved, the treatment concept can be considered as a (therapeutic) vaccine, and may lead to the cure of the disease as opposed to transient suppression of symptoms.
During infection or upon administration of HSP (peptides), the HSPs are taken up by antigen presenting cells (APC’s; dendritic cells in particular) and presented via binding to MHC class II molecules to T cells (Figure 1a). Only specific T cell subsets are activated this way and can differentiate into regulatory T cells. These cells are characterized by an increased production of IL-10 and/or other anti-inflammatory cytokines (Figure 1b).