Tumor-derived exosomes have been regarded as a new kind of
cancer vaccine; however, their therapeutic efficacy needs to be further improved.
Superantigen staphylococcal enterotoxin A (SEA)-coated
tumor cells have been shown to potently induce
tumor-specific T cell response. To increase efficacy of
tumor-derived exosomes to induce antitumor immune response, we modified the exosomes by
protein transfer of SEA tailed with a highly hydrophobic transmembrane domain (SEA-TM) and designated those SEA-TM-anchored exosomes as Exo/SEA-TM. We found the exosomes secreted from murine
lymphoma E.G7-OVA cell line were round vesicles with the sizes of 40-100 nm limited by a bilayer membrane. Interestingly, the inner structure of the exosomes were visible under the transmission electron microscope; those "honeycomb-like" inner structure has not been described by other labs. Immunization with Exo/SEA-TM inhibited
tumor growth and prolonged survival of the mice challenged with parental
tumor cells more significantly than with exosomes (Exo) and even more than with the mixture of exosomes and SEA-TM. The results of mixed lymphocyte-
tumor reaction (MLTR) showed that the increased
IL-2, IFN-gamma secretion, and specific cytotoxic T lymphocyte (CTL) could be effectively induced from the splenic lymphocytes of the mice immunized with Exo/SEA-TM. In vivo depletion experiments showed that CD8(+) T cells are the main effector cells, and both CD4(+) T cells and NK cells are also involved in the antitumor effect of Exo/SEA-TM immunization. Therefore,
tumor-derived exosomes surface anchored with SEA-TM can efficiently induce
tumor-specific CTL thereby resulting in more potent inhibition of
tumor growth. Our data provide an efficient and novel approach to
tumor immunotherapy by
protein modification of
tumor-derived exosomes.