| Project/Area Number |
05807113
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Nagasaki University school of Medicine |
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Principal Investigator |
KOHARA Norihiro Nagasaki University School of Medicine Lecturer, 医学部, 講師 (40221238)
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| Co-Investigator(Kenkyū-buntansha) |
SHIKU Hiroshi Nagasaki University School of Medicine Professor, 医学部, 教授 (80154194)
KANEMATSU Takashi Nagasaki University School of Medicine Professor, 医学部, 教授 (40128004)
日浅 厚則 長崎大学, 医学部, 医員
永田 康浩 長崎大学, 医学部, 医員
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Oncogene / Cytotoxic T Lymphocytes / Peptide Antigen / Tumor Antigen / 原癌遺伝子 / c‐erbB2 / MHCクラスI / ペプチド / CTL |
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| Research Abstract |
Expression of a variety of proto-oncogenes is often enhanced in cancer tissues. This indicates that peptides derived from proto-oncogenes are possible candidates as targets for immunoprotection against cancer. In many instances however, they are non-mutated and therefore not cancer specific in the strict sense. In fact most wild type proto-oncogenes are expressed in normal tissues to variable extends. This prompted us to investigate whether nonmutated peptides of the proto-oncogene c-erbB-2 can be recognized by murine cytotoxic T cells (CTL).
BALB/c mice immunized with CMS17HE (a syngeneic fibrosarcoma line transfected with human c-erbB-2 c-DNA), but not with CMS17neo or CMS17 rejected another syngeneic sarcoma line transfected with human c-erbB-2, CMS7HE.Spleen cells from thus immunized mice were further sensitized in vitro with CMS17HE.They became cytotoxic for transfectants of human and murine c-erbB2(CMS7HE and CMS7ME), but not parental CMS7 and CMS7neo.
The activity was blocked by monoclonal antibodies for murine CD8^+ or K^d, but not for CD4^+, D^d, I-A^d. These CTL were reactive with L-cells (H-2^k) transfected with Kd and c-erbB-2 cDNA,and also SK-Br3, a human breast cancer line expressing c-erbB-2, transfected with K^d cDNA.A series of peptides opf human or murine c-erbB-2 compatible with the K^d motif was synthesized. The CTL were reactive with P1HTR( H-2^d) pulsed with three peptides, CP811-1 (T) (human c-erbB-2 derived), CP811-1 (A) (murine c-erbB-2 derived), and CP811-5(common for human and murine c-erbB-2). Spleen cells immunized in vivo and in vitro with syngeneic spleen cells pulsed with these peptides were cytotoxic for CMS17HE and/or CMS17ME.
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