Research Project
Grant-in-Aid for Scientific Research on Priority Areas
The aims of this research project are as follows. 1) to identify tumor-specific antigens strongly expressed in cancer tissues as compared with various normal tissues, 2) to investigate possible usefulness of these tumor antigens for diagnosis and treatment of cancers. In these five years of research period, we identified the following six tumor-specific antigens useful for the cancer diagnosis and/or therapy. 1) Glypican-3 (GPC3); GPC3 is an oncofetal antigen and a GPI-anchored membrane protein. GPC3 is strongly expressed in hepatocellular carcinoma (HCC) and melanoma, but not expressed in various normal adult tissues. The serum soluble GPC3 was detected in about 40% of patients with HCC as well as melanoma. It is worth to note that the patients with even early stage of these cancers were positive for serum GPC3. GPC3 peptide-specific and MHC class I-restricted CTLs could be generated by stimulation with GPC3 peptides of human peripheral blood mononuclear cells (PBMCs) in vitro or stim … More ulation of mice in vivo. The mice pre-immunized with bone marrow-derived dendritic cells (DCs) pulsed with the GPC3 peptides were protected from the growth of transplanted colon cancer cell line, C26 transfected with mouse GPC3, in a CD8^+ CTL-dependent manner. 2) Proliferation potential related protein (PP-RP); PP-RP is a nuclear protein co-localized with chromosome during mitosis. PP-RP is strongly expressed in esophageal cancer cells and moderate expression was observed in testis and placenta but not in many other normal tissues. Knock down of PP-RP gene expression by RNAi inhibited the cell proliferation of esophageal cancer cell line, and the strong expression of PP-RP correlated with poor prognosis of the patients. Human CTLs could be generated by stimulation of PBMCs with PP-RP-derived peptides and these CTLs killed esophageal cancer cell line both in vitro and in vivo in nude mice transplanted with human cancer cells. 3) KM-HN-1, HSP-105, CLP and KM-PA2 ; these antigens were identified by SEREX method using cancer patients sera and cDNA expression libraries established from cancer cells or testis. These antigens are strongly expressed in several types of cancer cells and in several normal tissues at a lower level. CTLs specific to peptides derived from these antigens were generated and they killed cancer cells in both human and mice. 4) Embryonic stem (ES) cell-derived DC vaccine; we succeeded in augmentation of anti-tumor immunity by immunization of mice with ES cell-derived DCs expressing simultaneously genes encoding for an antigen and chemokines. Less
All 2005 2004 2003 2002 2001 2000
All Journal Article (92 results) Book (3 results) Patent(Industrial Property Rights) (9 results)
J.Immunol. 174
Pages: 1888-1897
Clin.Cancer Res. 10
Pages: 8630-8640
Pages: 6047-6057
Pages: 6612-6621
Pages: 6437-6448
J.Immunol. 172
Pages: 776-786
J.Biol.Chem. 279
Pages: 48457-48465
Mol.Immunol. 40
Pages: 1089-1094
Biochem.Biophys.Res.Comm 321
Pages: 432-440
Am.J.Cardiol. 93
Pages: 1547-1549
臨床免疫 42(1)
Pages: 110-114
実験医学 22(5)
Pages: 215-220
臨床免疫 41(4)
Pages: 369-378
医学をゲノムする(第27回阿蘇シンポジウム記録2003)
Pages: 115-127
Blood 101
Pages: 3501-3508
J.Immunol. 170
Pages: 947-960
Eur.J.Immunol. 33
Pages: 1497-1507
Circulation 107
Pages: 2196-2200
J.Invest.Dermatol 121
Pages: 1241
Biochem.Biophys.Res.Comm 306
Pages: 16-25
Clin. Cancer Res. 9
Pages: 5386-5393
Oncology reports 10
Pages: 1777-1782
Modern Rheumatology 10
Pages: 205-214
医学のあゆみ 207(8)
Pages: 543-548
J.Invest.Dermatol. 121
Biochem.Biophys.Res.Comm. 306
Clin.CancerRes. 9
Pages: 1777-82
Modern Rheumatology 13
Eur.J.Immunol. 32
Pages: 826-836
Biochem.Biophys.Res.Comm. 294
Pages: 734-741
Biochem.Biophys.Res.Comm. 290
Pages: 1022-1029
Immunol.Lts. 81
Pages: 149-155
Surgery Frontier 9(3)
Pages: 58-61
医学のあゆみ 200(6)
Pages: 467-471
Immunol. Lts. 78
Pages: 161-168
Biochem.Biophys.Res.Comm. 284
Pages: 1140-1147
Biochem.Biophys.Res.Comm. 281
Pages: 936-944
Eur.J.Immunol. 31
Pages: 563-572
Tissue Antigens 57
Pages: 447-456
Tissue Antigens 58
Pages: 395-401
Biochem.Biophys.Res.Comm. 280
Pages: 1169-1176
Clin.Exp.Immunol 31
Pages: 1126-1134
Modern Rheumatology 11
Pages: 103-112
学術月報 54(7)
Pages: 685-689
Immunol.Lts. 78
Eur.J.Immunol 31
Clin.Exp.Immunol. 31
Mol.Cell Biol. 20
Pages: 6195-6200
J.Biol.Chem. 275
Pages: 34998-35005
J.Immunol. 165
Pages: 83-90
Hepatology 32
Pages: 901-909
Biochem.Biophys.Res.Comm. 272
Pages: 456-465
Tissue Antigens 55
Pages: 199-205
Human Immunol. 61
Pages: 366-377
Am.J.Hematol. 63
Pages: 99-101
Mod. Rheumatol. 10
Pages: 235-239
分子細胞治療,特集:がん免疫療法の最前線 1(1)
Pages: 14-22
蛋白質・核酸・酵素 45(7)
Pages: 1205-1218
Mod.Rheumatol. 10