Periodic Reporting for period 3 - Target to B-cure (Targeting auto-reactive B-cells by vaccination to cure human auto-immune disease)
Período documentado: 2024-01-01 hasta 2025-06-30
Approximately 9% of the world population is affected by an autoimmune disease. These diseases often lead to debilitating morbidities that may have an enormous impact on the quality of life. Likewise, they frequently result in loss of employment and long-term care and treatment needs that represent a considerable cost for society. Most human autoimmune diseases are chronic, incurable conditions in which current interventions address the symptoms rather than causes of disease. Several autoimmune diseases, such as scleroderma or SLE, also have a profound impact on life expectancy, reflected in standardized mortality ratio’s that are similar and even higher than for breast cancer. The greatest challenge in the area of chronic human autoimmune diseases is to develop treatments that can induce permanent cure. This challenge can only be reached by combining new methods aiming to eradicate the disease-causing cells and/or pathways, with studies aiming to understand the processes that lead to the breach of immune tolerance and the emergence of autoimmunity.
Many autoimmune diseases are characterized by autoantibodies and are remarkably responsive to B-cell targeted therapies, demonstrating that the autoreactive B-cell is central to disease pathogenesis. Nonetheless, the selective and permanent elimination of the autoreactive B-cell, is not presently feasible due to a lack of specific markers and treatments. The aim of the project is to develop a vaccine that will allow the specific and long-lasting depletion of autoreactive B-cells, thereby inducing cure. This concept extends the remit of vaccines beyond infectious diseases and cancer, into the sphere of autoimmune disease. Using the well-defined autoimmune disease rheumatoid arthritis (RA) as prototype, we will study the RA-specific autoimmune response. Using recently developed technologies, we will identify autoreactive B-cells at several (pre)disease stages. Ultimately, we will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of specifically depleting disease-causing B-cells.
This research will create the possibility for patient-tailored vaccines that can permanently eradicate auto-reactive B-cells in B-cell driven auto-immune diseases; diseases that are still incurable to date.
Many autoimmune diseases are characterized by autoantibodies and are remarkably responsive to B-cell targeted therapies, demonstrating that the autoreactive B-cell is central to disease pathogenesis. Nonetheless, the selective and permanent elimination of the autoreactive B-cell, is not presently feasible due to a lack of specific markers and treatments. The aim of the project is to develop a vaccine that will allow the specific and long-lasting depletion of autoreactive B-cells, thereby inducing cure. This concept extends the remit of vaccines beyond infectious diseases and cancer, into the sphere of autoimmune disease. Using the well-defined autoimmune disease rheumatoid arthritis (RA) as prototype, we will study the RA-specific autoimmune response. Using recently developed technologies, we will identify autoreactive B-cells at several (pre)disease stages. Ultimately, we will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of specifically depleting disease-causing B-cells.
This research will create the possibility for patient-tailored vaccines that can permanently eradicate auto-reactive B-cells in B-cell driven auto-immune diseases; diseases that are still incurable to date.
We started studying the RA-specific autoimmune response. Our lab has extensive experience in investigation of the B cell biology and autoantibodies in RA. Cross-reactivity patterns of autoantibodies found in RA were established and autoreactive B cells were visualized by innovative technologies.
Although symptomatic treatment of human autoimmune disease has improved considerably, cure is still beyond the horizon. The next and most important challenge is therefore to achieve permanent cure. While autoreactive B-cells are at the center of disease pathogenesis, the selective and permanent elimination of these cells is currently not feasible. In this project we aim to explore a highly novel approach to reach permanent cure of a prominent autoimmune disease by developing a vaccine to deplete the autoreactive B-cell pool. Thereby, “Target to B-cure” will open a new field of patient-tailored vaccines that – if successful - can permanently eradicate auto-reactive B-cells in B-cell driven auto-immune diseases. Interventions that induce cure will have a major impact on individual patients, the healthcare system and society.