Analysis of expression of tumor-associated antigen, 90 K/Mac-2 binding protein (M2BP) in lung cancer and development of cancer immunotherapy targeting M2BP
| Project/Area Number |
14571262
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
FUJINO Shozo Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助教授 (10209075)
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| Co-Investigator(Kenkyū-buntansha) |
KONTANI Keiichi Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助手 (90314153)
TEZUKA Noriaki Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助手 (40303771)
SAWAI Satoru Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助手 (60335172)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | tumor antigen / immunotherapy / Mac-2 binding protein / lung cancer / 90K / 腫瘍関連抗原 / 癌免疫治療 / 90K抗原 / 免疫原性 / 癌免疫療法 |
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| Research Abstract |
We analyzed the expression of M2BP in lung cancer cells and its immunogenicity as a tumor antigen. Seven of the 8 (87.5%) cultured lung cancer cell lines and 17 of the 28 (60.7%) tumor tissues from patients with primary lung cancer were shown to express high levels of M2BP mRNA. The serum levels of antibodies to M2BP were elevated in 30.4% of the patients. Interestingly, M2BP-specific IgG was observed in all of the patients with anti-M2BP antibodies. Therefore, M2BP is highly expressed in lung cancer and that M2BP-specific immunity was observed in many of patients with lung cancer. These findings suggested the possibility of M2BP to use as a target antigen in cancer immunotherapy. CTLs were generated from peripheral blood lymphocytes of two HLA-A2-positive healthy donors by multiple stimulations in vitro with M2BP-derived peptides showing high affinity to HLA-A2. The CTLs induced using M2BP216-224 (RIDITLSSV) produced interferon-gammain response to HLA-A2-positive T2 cells pulsed with this peptide. Also, the CTLs exhibited specific lytic activity against not only peptide-pulsed T2 cells but also MDA-MB-231 cells expressing both M2BP and HlA-A2. The cytolytic activities were blocked by adding antibodies against HLA class I or CD8 but not by antibodies against HLA class II or CD4. These data suggested that M2BP216-224 is naturally processed from the native M2BP molecule in cancer cells and recognized by M2BP-specific CTLs in an HLA-A2 restriction. We first identified the CTL epitope derived from M2BP and it is expected to be useful as a target antigenic epitope in clinical immunotherapy of lung cancer.
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Report
(3 results)
Research Products
(4 results)
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[Publications] Y.Ozaki, K.Kontani, J.Hanaoka, T.Chano, K.Teramoto, N.Tezuka, S.Sawai, S.Fujino, T.Yoshiki, H.Okabe, I.Okubo: "Expression and immunogenicity of tumor-associated antigen, 90K/Mac-2 binding protein, in lung carcinoma. The possibility of its clinical use as a tumor marker and a target antigen in cancer immunotherapy"Cancer. 95. 1954-1962 (2002)
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