Currently, only one tuberculosis (TB) vaccine is available: Mycobacterium bovis Bacille Calmette-Gu_rin (BCG). This vaccine induces highly variable protection against pulmonary TB, the most common... Show moreCurrently, only one tuberculosis (TB) vaccine is available: Mycobacterium bovis Bacille Calmette-Gu_rin (BCG). This vaccine induces highly variable protection against pulmonary TB, the most common and contagious form of TB. There is an urgent need for an effective TB vaccine which is safe also in the immunocompromised host. The main focus of this thesis was to identify Mycobacterium tuberculosis (Mtb) infection phase related antigens and to evaluate these as potential antigens for TB vaccines. The studies presented in this thesis describe: (i) the immunogenic potential of two previously described sets of antigens; resuscitation promoting factor (Rpf) and dormancy regulon encoded (DosR) antigens, (ii) the identification and immunogenicity of a third set of antigens known as in vivo expressed Mtb (IVE-TB) antigens, (iii) the protective value of IVE-TB antigen Rv2034 and (iv) the analysis of Rv2034-specific T cell r esponses at the clonal level. Together, these data illustrate the vaccine potential of infection phase related antigens. Show less
Skin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the... Show moreSkin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the high and rising prevalence of cutaneous SCC puts an increasingly high financial burden on society, marking a pressing need for advancements in skin cancer drug development. For screening of novel therapeutics, representative models of human cutaneous SCC are required. The aim of the research described in this thesis was to develop a representative in vitro model of human SCC for screening therapeutics, without the unnecessary use of animals. To this end, we generated three-dimensional in vitro SCC models in which the malignant epidermal cancer cells were either represented by intact primary human cutaneous or by established, spontaneously immortalized cutaneous SCC cell lines. The dermal microenvironment in our models was seeded with either primary normal human dermal fibroblasts or primary SCC-associated fibroblasts. In verifying human cutaneous SCC representation by these in vitro models, we focused on hyperproliferation, cytological and architectural atypia and invasion as three main features of primary SCC. The in vitro skin cancer models presented in this thesis add to the spectrum of available in vitro models for therapeutic screening. Show less