Cancer is a leading cause of death worldwide and cancer vaccination might be a promising strategy to prevent or block tumour growth and metastasis. For this purpose it is key to target tumour-specific antigen to antigen presenting cells of our immune system and to activate the immune system in such a way that killer T-cells are generated, which can recognize and eliminate malignant cells. Unfortunately, common vaccine formulations comprising soluble protein antigen and commonly applied adjuvants, such as aluminium hydroxide, merely offer a depot effect and predominantly evoke a humoral (antibody
mediated) immune response and no killer T-cells.
Microparticles offer a powerful tool to target antigen and immune-modulating compounds to dendritic cells which are actively phagocyting cells that continuously sample and present antigen. As dendritic cells have evolved to react to viruses and bacteria, which are of particulate nature, particles with sizes from 100 nm to 10 μm are efficiently taken up by these cells. Moreover, particulate antigen formulation are known to induce ‘cross-presentation’, which is a crucial step in the induction of killer T-cell and does not occur in case of soluble antigen. Furthermore, microparticulate encapsulation strategies also allow to co-encapsulate immune-modulating components, which can steer the immune response in a specific direction.
In this project we aim to develop a generic microparticulate encapsulation platform by formulating tumour specific antigens with biocompatible synthetic polymers which are decorated with immunemodulating motifs that steer the immune response in the direction of killer T-cells. Evaluation of the developed formulations will be performed in vitro and in vivo in mice tumour models for Lewis Lung carcinoma.