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
In this book liposomes are explored as delivery system for allergen-specific immunotherapy. Both cationic and anionic formulations are prepared with Bet v 1, one of the allergens in birch pollen... Show moreIn this book liposomes are explored as delivery system for allergen-specific immunotherapy. Both cationic and anionic formulations are prepared with Bet v 1, one of the allergens in birch pollen.Moreover, a novel method is described which can be used to associate antigens with liposomes. This method is based on coiled-coil forming interaction of two complementary peptides. Show less
Synthetic long peptides (SLP) derived from cancer-associated antigens hold great promise as well-defined antigens for cancer immunotherapy. Clinical studies showed that SLP vaccines have... Show more Synthetic long peptides (SLP) derived from cancer-associated antigens hold great promise as well-defined antigens for cancer immunotherapy. Clinical studies showed that SLP vaccines have functional potency when applied to pre-malignant stage patients, but need to be improved for use as a therapeutic intervention against tumours. So far, SLPs have been administered in Montanide ISA-51, a water-in-oil formulation with reported important drawbacks and induced local side effects. Therefore, there is an urgent need for replacement of Montanide by more potent and safe alternatives. In this thesis, the concept of cationic liposome-based formulations was introduced, as the backbone for improved delivery of SLPs for cancer therapeutic vaccination. The developed formulation’s ability to induce efficient immune responses able to control tumour outgrowth in aggressive independent tumour models, makes cationic liposomes a very promising platform for SLP-based cancer immunotherapy. Their flexibility regarding the properties of loaded SLPs, their relative inexpensive production and the possibility to administer them via different delivery routes are all in favour for liposomal SLP-based cancer immunotherapy to become reality soon. Show less
