Exosomes: a new delivery system for tumor antigens in cancer immunotherapy.
Exosomes are small membrane vesicles that are released into the extracellular environment during fusion of multivesicular bodies with plasma membrane. Exosomes are secreted by various cell types including hematopoietic cells, normal epithelial cells and even some tumor cells. They are known to carry MHC class I, various costimulatory molecules and some tetraspanins. Recent studies have shown the potential of using native exosomes as immunologic stimulants. Here, we demonstrate a novel means of using exosomes engineered to express a specific tumor antigen to generate an immune response against tumors. We expressed a target tumor antigen, human MUC1 (hMUC1), in 2 MHC type-distinct mouse cell lines, CT26 and TA3HA. Analysis of exosomes purified from these cells revealed that exosomes contained the target MUC1 antigen on their surfaces as well as other well-described exosomal proteins, including Hsc70 and MHC class I molecules. In addition, both autologous and allogenic exosomes were able to stimulate the activation of immune cells and suppress hMUC1-expressing tumor growth in a MUC1-specific and dose-related manner. Therefore, these data suggest that exosomes can be engineered from tumor cell lines to deliver a target immunogen capable of inducing an effective immune response and that they may represent a new cell-free tumor vaccine.
Cho
Jung-Ah
JA
Department of Pathology, Tumor Immunity Medical Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Yeo
Dong-Jun
DJ
Son
Hye-Youn
HY
Kim
Hyun-Wha
HW
Jung
Dae-Sun
DS
Ko
Jae-Kyun
JK
Koh
Jason Soonju
JS
Kim
Yong-Nyun
YN
Kim
Chul-Woo
CW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D019496:Cancer Vaccines; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018396:Mucin-1 / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D018396:Mucin-1; D009363:Neoplasm Proteins; D010455:Peptides; D007371:Interferon-gamma