Trajectum Pharma B.V. is a bio-pharmaceutical company based in Utrecht (the Netherlands). The company was founded on July 15th, 2010 as a spin-out of the Department of Infectious Diseases & Immunology of Utrecht University.

The company is developing new therapies for inflammatory diseases, more specifically therapeutic vaccines for rheumatoid arthritis and inflammatory bowel disease. In addition the company is developing assay systems for the monitoring of vaccine safety, in particular with respect to autoimmunity and assay systems for the in vitro detection of immunogenicity.

Recently Trajectum Pharma has embarked on the approach to establish tolerance in RA patients using tolerizing Dendritic Cells (tolDC) loaded with HSP70 peptide B29.

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 self-controlling system by actively immunizing with B29, which has been shown to induce regulatory T cells in vivo. 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.

The immune balance is restored.

Thus, the basic principle that underpins the therapy is to educate tolerance-invoking regulatory T-cells. An orchestrated series of events need to happen to achieve this, and hence to allow it to be an effective approach to treatment of RA.

➢ Tolerogenic B-29-specific Treg-cells are present in the patient, which is verified with our assay.
➢ The patient is treated with anti-TNF (or similar) to induce a state of disease remission.
➢ Dendritic cells are obtained from the patient ①, using standardized protocols.
➢ The dendritic cells are ex-vivo primed with B-29 ②, so that they can present this epitope to Treg.
➢ The cells are re-introduced into the patient ③ (remission allows for better tolerance induction).
➢ The epitope is presented to Treg-cells by the dendritic cells ④, to activate the tolerogenic cells.
➢ The patient now has a Treg repertoire that naturally suppresses inflammation ⑤ (in the joint).