HCR.20.026 – Innovative immunotherapy: inducing tolerance to autoimmunogenic antigens and allergens

Route: Health care research, sickness prevention and treatment

Cluster question: 096 How can we improve diagnostics, treatment, and vaccines for immunodeficiencies and infectious diseases?

Auto-immune disorders pose a major worldwide issue with rising prevalence. To date, dozens of immune-based therapies have emerged aiming to prevent and reverse the disorder. Difficulties in achievement of this goal have been plentiful, and can be attributed to inadequate addressing of immunologic contributions to the disease.
DC4U has an advanced technology involving glycans (the GlycoDCTM platform), which can be applied to vastly improve existing immunotherapies. The platform enables development of highly effective treatments, based on the induction of tolerance to the auto-antigens involved in immune diseases. The essence of the GlycoDCTM technology is the application of the natural glycobiology to reprogram the immune response to a specific autoantigen. By direct linkage immune suppression-associated sialic acid glycans to the antigens, the platform functions as an endogenous recognition element for the immune system. Dendritic cells, that play a central role in the immune system, read these elements as a negative immune activation signal, and direct the adaptive immune response accordingly. This project will complete the validation of the GlycoDCTM platform and enables a proof-of-concept for autoimmune disorders Celiac Disease (CD) and Diabetes Mellitus type-I (DM). Treatment of both disorders comprise mainly of symptom control, whereas treatments to restore the immune balance still have not reached the market.
The novel immune therapy developed here derives from constructs from the LUMC portfolio. At the LUMC, the endogenous auto-antigens for CD and DM have been well-characterized and assessed in patients. DC4U will couple the GlycoDCTM platform to the most immunodominant antigens and assess with the AmsterdamUMC and LUMC the induced responses in vivo and by patient cells. The collaboration with Janssen (JPNV) enables guidance and strategic decision making towards clinical trials. This innovation will provides a key showcase product for Janssen’s ‘World Without Disease Accelerator (WWDA)’ a new program focusing on the prevention and cure of childhood diseases.

Keywords

allergy, auto-immunity, Celiac Disease, Diabetes Mellitus, glycans, Immunotherapy, Tolerance

Other organisations

DC4U BV, Janssen Pharmaceuticals, Leiden Universitair Medisch Centrum (LUMC)

Submitter

Organisation AmsterdamUMC - location Vumc (VUMC)
Name Prof. dr. Y. (Yvette) van Kooyk
E-mail Y.vankooyk@amsterdamumc.nl
Website https://www.vumc.nl/research/overzicht/molecular-cell-biology-immunology-research/principal-investigators/yvette-van-kooyk.htm