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Publication

Targeted tolerance in multiple sclerosis

Book - Dissertation

Subtitle:development of transgenic T cell receptor-engineered regulatory T cells recognizing myelin-derived antigens
Given the increase in global mean prevalence of MS and other autoimmune disease, and the unmet medical need, the quest for new disease-specific treatments continues. In the last decennia, the regulatory mechanisms of the immune system were exploited therapeutically to reshape immune responses and induce durable immune tolerance. Also, adaptive regulatory T cell (Treg) therapy has found its way to the clinic with dozens of clinical trials ongoing and finished. To date, researchers seek to augment clinical efficacy by using a broad range of molecular engineering methods with the first clinical trials using engineered Tregs ongoing. The general aim of this thesis was to develop a clinically safe vaccine for the treatment of MS, based on Tregs specifically targeting cells involved in the onset and progression of the disease. In addition, we provide an alternative for currently used engineering methods, which have shown pre-clinical efficacy and thus clinical potential, but also possess multiple safety concerns. In doing so, we aimed to advance the field of Treg therapy by providing in vitro proof of TCR-encoding mRNA-transfected Tregs and we are convinced that the work presented in these thesis will play its part in the road to long-lasting tolerance in MS and other autoimmune diseases.
Number of pages: 272
ISBN:978-94-6458-856-9
Publication year:2023
Keywords:Doctoral thesis
Accessibility:Open