This thesis describes the development and immunological evaluation of two different cancer vaccination strategies for peptide-based personalized cancer vaccines. Both strategies, liposomal... Show moreThis thesis describes the development and immunological evaluation of two different cancer vaccination strategies for peptide-based personalized cancer vaccines. Both strategies, liposomal encapsulation and adjuvanting by direct conjugation to a TLR-ligand, are aimed to be readily combined with neoantigen-containing synthetic peptide sequences. In order to formulate such personalized cancer vaccines a flexible platform is required that can harbor a wide range of physiochemically different SPs, because multiple neoepitopes are uniquely expressed per patient. Upon formulation, the vaccination platform should be able to induce effective tumor-specific immune responses, which was evaluated in this thesis in in vitro and in vivo preclinical models. Show less
Type 1 diabetes (T1D) results from the immune-mediated destruction of the insulin-producing beta cells. Genetic predisposition, impaired immune regulation, and beta cell (dys)function all... Show moreType 1 diabetes (T1D) results from the immune-mediated destruction of the insulin-producing beta cells. Genetic predisposition, impaired immune regulation, and beta cell (dys)function all contribute to disease initiation and progression. A critical gap in our knowledge is what causes the break in peripheral tolerance that eventually leads to beta cell destruction. We propose that neoepitopes generated by dysfunctional beta cells activate immune surveillance, causing beta cell autoimmunity. ER stress imposed both by intrinsic beta cell physiology and by external secondary triggers seems to be a crucial component in this process. Understanding the molecular mechanisms underlying beta cell dysfunction and neoantigen generation is critical to identify clinically relevant neoepitopes. This subsequently provides more insight in the disease dynamics as well as contribute to translational research in the development of biomarker assays and development of therapeutic strategies targeting autoreactive T-cells and beta cell function. Our task will be to restore the balance between immune reactivity and beta cell function, in order to prevent, treat, or cure type 1 diabetes. Show less