| Project/Area Number |
12213111
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University |
|---|
Principal Investigator |
NISHIMURA Yasuharu Kumamoto University, Department of Immunogenetics, Graduate School of Medical Sciences, Professor, 大学院医学薬学研究部, 教授 (10156119)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SENJU Satoru Kumamoto University, Department of Immunogenetics, Graduate School of Medical Sciences, Associate Professor, 大学院医学薬学研究部, 助教授 (50274709)
NAKATSURA Tetsuya Kumamoto University, Department of Immunogenetics, Graduate School of Medical Sciences, Research Associate, 大学院医学薬学研究部, 助手 (30343354)
入江 厚 熊本大学, 大学院・医学研究科, 助手 (30250343)
|
|---|
| Project Period (FY) |
2000 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥52,200,000 (Direct Cost: ¥52,200,000)
Fiscal Year 2004: ¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2003: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2001: ¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
|
|---|
| Keywords | Tumor-specific antigens / Tumor markers / Anti-tumor immunity / Cytotoxic T lymphocytes / Antigenic epitopes / cDNA microarray analysis / Serex method / Hepatocellular carcinoma / Melanoma (CONTINUE TO NEXT PAGE) / 腫瘍抗原 / 細胞障害性T細胞 / ヘルパーT細胞 / T細胞エピトープ / SEREX法 / 細胞傷害性T細胞 / 膵癌 / SEREX / 抗原ペプチド / IgG / 微生物ペプチド / 交叉反応性 / 抗腫瘍抗体 / 遺伝子発現クローニング / 膵臓癌 / 大腸癌 / hsp105 |
|---|
| Research Abstract |
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
|
