Extracellular vesicles and their current role in cancer immunotherapy

Extracellular vesicles are lipid bilayer-delimited particles released into the extracellular environment by different cell types under both physiological and pathological conditions. Based on their size and biogenesis’ mechanism, they can be classified into three groups: microvesicles, apoptotic bodies and exosomes. The extracellular vesicles are characterized by a very heterogeneous molecular composition; therefore, they are involved in numerous biological processes including intercellular communication. Indeed, they act as natural carriers in the transfer of biomolecules such as DNA, RNA, proteins, lipids and metabolites. Thanks to the transfer capacity and the possibility of targeting target cells, they can be employed in drug and gene delivery for the treatment of cancer and various diseases. In recent years, the use of vesicles as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of extracellular vesicles to transport molecules capable of triggering an immune response to damage cancer cells. In particular, several studies have analysed the possibility of using extracellular vesicles in the new cancer vaccines, which represent a particular form of immunotherapy. Currently, in the literature there are no publications that systematically collect the studies made on therapeutic anticancer vaccines based on extracellular vesicles. Therefore, the purpose of this work is to illustrate some of the most indicative clinical studies, completed or still in progress, and to give a partial reorganization of what has been produced in the literature so far. The first part of this thesis provides a general overview of extracellular vesicles and adequate isolation methods in order to obtain extracellular vesicles capable of carrying a therapeutic load. The second part focuses on which kind of molecules can be loaded into the extracellular vesicles and provides a broad description of cargo-loading methods. At the same time, several examples from the literature are displayed to show the variety of studies carried out in the field of gene and drug delivery. Finally, some engineering techniques aimed at introducing specific surface markers for cell targeting are reported. The last part contains the primary purpose of this thesis; therefore, it provides basic notions on cancer immunotherapy and describes several clinical trials in which therapeutic anticancer vaccines are tested. The ultimate aim of this work is to highlight the potential of extracellular vesicles-based therapeutic vaccines in the treatment of cancer patients, even with advanced stage-cancer.