Modulation of tumor-derived exosomes for an efficient cancer vaccine

3443 Exosomes are small membrane vesicles secreted from a various kinds of cells including hematopoietic cells, normal epithelial cells and some tumor cells. Like APC-derived exosomes, tumor-derived exosomes also possess the potential of immunologic stimulants because they harbor native tumor antigens as well as immunologically significant molecules like MHC class I and Hsc70. Nevertheless, tumor-derived exosomes can possess tolerogenic properties because of characteristics of tumor cells on their own. Therefore, we attempted to generate more immunostimulatory tumor-derived exosomes. First, we introduced a common tumor antigen MUC1 into tumor cell lines to make a broadly-applicable cancer vaccine. The data showed that exosomes from the trasnduced tumor cells harbored MUC1 and produced MUC1-specific anti-tumor effect in vivo. Secondly, we conjugated exosomes to oxidized mannan in order to augment a possibility to be targeted to dendritic cells and observed that mannan conjugation to exosomes efficiently enhanced internalization of exosomes by antigen-presenting cells. Thirdly, tumor cells were heat-treated to recruit more heat shock proteins into exosomes, which increased immune stimulus can be expected. During the recovery times after heat shock, inducible Hsp70 were highly expressed and appeared at the cellular surfaces. Simultaneously, exosomes from heat-treated tumor cells harbored the inducible form of Hsp70 and the quantity of exosomes were increased by heat treatment. These data suggest that exosomes can be modulated to become more immunogenic and may represent a first demonstration of modulated tumor-derived exosomes in using in cancer therapy.