Exosomes as a model of "natural nanoparticles" for the identification of novel anti-tumor therapies

• Applicant: Dr. Maja Bürdek
• Subject Area: Hematology, Oncology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198700196

Exosomes are small vesicles derived from endosomes and secreted from different cell types, like dendritic cells, lymphocytes and epithelial cells. They may carry MHC (major histocompatibility complex) proteins, proteins involved in antigen presentation as well as membrane and cytosolic proteins. Interestingly, tumor cells show an exacerbated release of exosomes through a constitutive pathway. Exosomes secreted from tumor cells are known to contain tumor-associated antigens, which are antigens that are over-expressed in tumor cells but only weakly expressed in normal cells. Therefore these antigens represent a promising target for anti-tumor immunotherapy. It has already been shown that antigens present in exosomes can be presented to T cells via crosspresentation by antigen-presenting cells. I will examine whether MHC/antigen complexes expressed in tumor exosomes can also directly interact with T cells. What is more, I will verify whether exosomes can serve as a source of MHC/antigen complexes for direct activation of naïve T cells in an allogeneic priming approach in vitro. In this priming approach, naïve, HLA-A2 negative, cytotoxic T cells will be stimulated with exosomes derived from HLA-A2 positive tumor cells. Using this method it is possible to obtain antigen-specific, high-avidity T cells that have not undergone the process of negative selection.Another goal will be the analysis of the expression of pro-apoptotic molecules, like TRAIL (TNF related apoptosis inducing ligand), in exosomes. It has already been shown that tumor cells release exosomes containing pro-apoptotic molecules, like FasL (Fas Ligand), thereby inducing apoptosis in T lymphocytes. On the other hand, TRAIL-expressing exosomes could represent a cell-free tool to deliver death signals to tumor cells. I will examine whether TRAIL-expressing exosomes can induce apoptosis in tumor cells without affecting other cell types.

• DFG Programme: Research Fellowships
• International Connection: Italy
• Host: Dr. Licia Rivoltini