Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells.
We recently established a novel drug delivery system (DDS) using oligomannose-coated liposomes (OMLs) which are probably taken up by macrophages (Mvarphi) to carry anti-cancer drugs to milky spots known as preferential metastatic sites of gastric cancers [Y. Ikehara, T. Niwa, L. Biao, S.K. Ikehara, N. Ohashi, T. Kobayashi, Y. Shimizu, N. Kojima, H. Nakanishi, A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle, Cancer Res. 66 (2006) 8740-8748]. In the present study, we applied this intraperitoneal DDS for systemic cancer immunotherapy employing ovalbumin (OVA) as a model antigen. The cells taking up the OMLs containing FITC-OVA injected into the peritoneal cavity were predominantly Mvarphi, as they showed adhesive characteristics and expressed F4/80 and CD11b almost exclusively. The phagocytic cells also took up bare OVA directly to the same extent as OML-enclosed OVA (OML-OVA), as it is a highly mannosilated protein. The phagocytic cells taking up OML-OVA, however, could activate OVA-specific CD8+ (from OT-I: H-2Kb/OVA257-264-specific) and CD4+ (from OT-II: H-2Ab/OVA323-339-specific) T cells much more effectively in vitro than those taking up bare OVA. Furthermore, only the mice pre-immunized with OML-OVA rejected E.G7-OVA (OVA-transfected EL4) but not EL4. These results indicate that the OMLs can also be used as an effective antigen delivery system for cancer immunotherapy activating both CTL and Th subsets.
Ikehara
Yuzuru
Y
Molecular Medicine Team of Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Centeral 2-12, Room 211, 1-1-1 Umezono, Tsukuba, Japan. yuzuru-ikehara@aist.go.jp
Shiuchi
Nobumitsu
N
Kabata-Ikehara
Sanae
S
Nakanishi
Hayao
H
Yokoyama
Naoaki
N
Takagi
Hideaki
H
Nagata
Toshi
T
Koide
Yukio
Y
Kuzushima
Kiyotaka
K
Takahashi
Toshitada
T
Tsujimura
Kunio
K
Kojima
Naoya
N
D000818:Animals; D017951:Antigen Presentation; D000943:Antigens, Differentiation / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D002465:Cell Movement; D004337:Drug Carriers; D004339:Drug Compounding; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D016056:Immunodominant Epitopes; D007167:Immunotherapy / Q000379:methods*; D008081:Liposomes; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010587:Phagocytosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013945:Thymoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013953:Thymus Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D014312:Trisaccharides / Q000737:chemistry / Q000378:metabolism*
D000943:Antigens, Differentiation; D039481:CD11b Antigen; D004337:Drug Carriers; D004527:Egg Proteins; D006183:H-2 Antigens; C489629:H-2A(b) antigen, mouse; C032876:H-2Kb protein, mouse; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D008081:Liposomes; C111390:OVA 323-339; C110366:OVA-8; D010446:Peptide Fragments; D014312:Trisaccharides; C036763:monocyte-macrophage differentiation antigen; C023872:mannotriose; D010047:Ovalbumin