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Identification of non-mutated c-erbB-2 derived peptides recognized by murine CD8+ cytotoxic T cells

Research Project

Project/Area Number 05807113
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionNagasaki University school of Medicine

Principal Investigator

KOHARA Norihiro  Nagasaki University School of Medicine Lecturer, 医学部, 講師 (40221238)

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
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
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)
KeywordsOncogene / Cytotoxic T Lymphocytes / Peptide Antigen / Tumor Antigen / 原癌遺伝子 / c‐erbB2 / MHCクラスI / ペプチド / CTL
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.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Nagata,Y.,et al.: "Establishment and charactqrization of human gallbladder adenocarcinoma cell line with c-erbB-2." Proceeding of the Japanese Cancer Association. 52. 269 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata,Y.,et al.: "Induction and specificity of CTL for c-erbB-2 transfected cells." Proc.Jpn,Soc.Immunol.23. 513 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata,Y.,et al.: "Induction and specificity of CTL for c-erbB-2 transfected cells." Proceeding of the Japanese Cancer Association. 53. 413 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata,Y.,et al.: "Induction of cytotoxic T cells (CTLs) against c-erbB-2 oncogene products." Biotherapy. 9(5). 670-671 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Furugen,R.,et al.: "Induction and amplification of anti-tumor T cell responses by sensitization with c-erbB-2 derived peptides." Proceeding of the Japanese Cancer Association.54. 1435 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata, Y., et al: "Establishment and charactarization of human gallbladder adenocarcinoma cell line with c-erbB-2." Proceeding of the Japanese Cancer Association. 52. 269 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata, Y., et al: "Induction and specificity of CTL for c-erbB-2 transfected cells." Proc.Jpn.Soc.Immunol.23. 513 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata, Y., et al: "Induction and specificity of CTL for c-erbB-2 transfected cells." Proceeding of the Japanese Cancer Association. 53. 413 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagata, Y., et al: "Induction of cytotoxic T cells (CTSs) against c-erbB-2 oncogene products." Biotherapy. 9(5). 670-671 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Furugen, R., et al: "Induction and amplification of anti-tumor T cell responses by sensitization with c-erbB-2 derived peptides." Proceeding of the Japanese Cancer Association.54. 1435 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yamaguchi,J.,etal: "Long-term survival of orthotopic lewis liver grafts in wistar furth rats." Transplantion. 5. 412-428 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hua Yang,et al: "Oligoclonal expansion of CD8+ T lymphocytes in cultured peripheral lymphocytes derived from asymptomatic HTLV-I carriers." Int.J.Oncol.5. 159-167 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshimura,A.,et al: "GD2 ganglioside-specific monoclonal antibody reacts with murine cytotoxic T lymphocytes reactive with FBL-3N erythroleukamis." Scand J.Immunol.40. 557-563 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Furukawa,K.,et al: "Clonal expansion of CD8+ cytotoxic T lymphocytes against human T cell lymphotropic virus type I (HTLV-I) genome products in HTLV-I associated myelopathy/tropical spastic paraparesis patients." J.Clin.Invest.94. 1830-1839 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamada,Y.,et al: "Established IL-2-dependent double-negtive (CD4-CD8+) TCR αβ/CD+ ATL cells : induction of CD4 exprssion." British J.of Haematology. 88. 234-241 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suto R.: "Effect of accessory cells on stimulation of murine T‐cell leukemia with antibodies to the CD3/T cell antigen receptor complex." Jpn.J.Cancer Res.84. 438-444 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshimura A.: "Rejection of an IA^+ variant line of FBL‐3 leukemia by cytotoxic T‐lymphocytes with CD4^+ and CD4^-CD8^- T‐cell receptor alphabeta phenotypes generated in CD8‐depleted C57BL/6 mice." J.Immunol.150. 4900-4910 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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