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癌遺伝子産物由来ペプチド抗原による癌治療

Research Project

Project/Area Number 09255220
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionMie University

Principal Investigator

珠玖 洋  三重大学, 医学部, 教授 (80154194)

Project Period (FY) 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 1999: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1998: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1997: ¥10,000,000 (Direct Cost: ¥10,000,000)
Keywords抗原ペプチド / HER2 / CTL / 腫瘍抗原 / SEREX / 抗遺伝子 / ペプチド / 癌抗原 / MAP Kinase / 腫瘍拒絶抗原
Research Abstract

1.4株のBALB/cマウス由来メチルコラントレン誘発肉腫、CMS2、CMS7、CMS8、CMS13担癌マウス血清中のIgG抗体により認識される抗原支配遺伝子を、腫瘍細胞より作製されたλファージcDNAライブラリーを用いたexpression cloning法で単離した。CMS2から42個、CMS7から9個、CMS8から41個、そしてCMS13からは43個のクローンを単離した。
2.ヒトHER2のN末端より147個のアミノ酸を含む組み替えHER2蛋白を作製し、コレステロール基により疎水化された多糖類プルランとの複合体(CHP-HER2)を作製した。本複合体で前処置されたHLA-A2402陽性樹状細胞は、HER2p63ペプチド特異的CTLクローンにより殺傷され、またそれらの樹状細胞は同CTLクローンを特異的に刺激した。また、CHP-HER2前処置細胞によるHER2p63ペプチドの提示は、内在性蛋白由来MHCクラスI結合性ペプチド提示と同様の機構によることが明らかとなった。
3.CHP-HER2免疫マウスの膝窩リンパ節由来リンパ球のin vitro刺激を繰り返し、CD4^+T細胞ラインを作製した。それらの特異性の解析より、HER2組み替え蛋白中(147アミノ酸)には少なくとも3個のヘルパーエピトープが含まれていることが明らかとなった。

Report

(3 results)
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Wang L., Ikeda H., Ikuta Y., et al.: "Bone marrow-derived dendritic cells incorporate and process hydrophobized polysaccharide/oncoprotein complex as antigen presenting cells"Int. J. Oncol.. 14. 695-701 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zhao, J., Furukawa, K., Fukumoto, S., et al.: "Attenuation of interleukin 2 signal in the spleen cells of complex ganglioside-lacking mice"J. Biol. Chem.. 274. 13744-13747 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki, Y., Yamamoto, M., Wada, H., et al.: "Agonist-induced regulation of myosin phosphatase activity in human platelets through activation of Rho-kinase"Blood. 93. 3408-3417 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohmi, Y., Shiku, H., and Nishimura, T.: "Tumor-specific targeting of T helper type 1(Th1) cells by anti-CD3x anti-c-ErbB-2 bispecific antibody"Cancer Immunol. Immunother.. 48. 456-462 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamaguchi, M., Ohno, T., Oka, K., et al.: "De novo CD5-positive diffuse large B-cell lymphoma : clinical characteristics and therapeutic outcome"Br. J. Haematol.. 105. 1133-1139 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shikami, M., Miwa, H., Nishii, K., et al.: "Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukemia cells with t(16;21)(p11;q22) : frequent expression of CD56 and interleukin-2 receptor alpha chain"Br. J. Haematol.. 105. 711-719 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miwa,H.,et al: "Biphasic expression of CD4 in acute myeiocytic leukemia(AML)cells : AML of monocyte origin and henatopoietic precursor cell origin" Leukemia. 12. 44-51 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Gu,X-G.,et al: "A novel nydrophopized polysaccharide loncoprotein complex vaccine induces in vitro and in vivo cellular and humoral imnune responses against HER2 expressing murine sarcomos" Cancer Res.58. 3385-3390 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Katayama,N.,et al: "Granulocyte colony-stimulating factor and its receptor in acute promyelocytic leukemia" Amer.J.Hematol.58. 31-35 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taniguchi,M.,et al: "De noro CD5^+ diffuse large B-cell lymphomas express VH genes with somatic mutation" Blood. 91. 1145-1151 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Katayama,N.,et al: "Role for C-MP2 and its ligand thrombopoietin in early hematopoiesis" Leuk.Lymphoma. 28. 51-56 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda,H., et al.: "Mutated MAP kinase,Atumor rejeotion antigen of mouse sarcoma" Proc.Natl.Acad.Sci.USA. 94. 6375-6379 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagata,T., et al.: "Peptides derived from a wild type murine proto-oncogene c-erB-2/HER/neu can induce CTL and tumor suppression in syngeneic hosts" J.Immunol. 159. 1336-1343 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Schmitt,M., et al.: "Involvement of T cell subsets and natural killer(NK)cells in growth suppression of murine fibrosarcoma cells transfected with interleukin-12(IL-1 genes)" Int.T.Caraer. 72. 505-511 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Murata.K., et al.: "In vivo retrovirus-mediated herpes simplex virus thymidine kinase gene therepy approach for adult T cell leulemia in a rat model." Jap J Cancer Res.88. 492-500 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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