1995 Fiscal Year Annual Research Report

ヒト自家癌拒絶の免疫学的分子機構

Research Project

Project/Area Number	07274112
Research Institution	Sapporo Medical University
Principal Investigator	菊地浩吉札幌医科大学, 医学部, 教授 (00045345)
Co-Investigator(Kenkyū-buntansha)	松浦晃洋札幌医科大学, 医学部, 講師 (70157238) 益子高東北大学, 薬学部, 助教授 (30157200) 伊東恭悟久留米大学, 医学部, 教授 (50125499) 別宮好文東大医科学研究所, 助手 (70199454) 笠原正典北海道大学, 医学部, 助教授 (30241318)
Keywords	腫瘍免疫 / 癌抗原ペプチド / 癌抗原提示分子 / クラスIb / T細胞レセプター / 癌遺伝子
Research Abstract	本研究は人癌とくにヒト固型癌の自家T細胞による免疫学的癌抗原認識、拒絶の分子機構を明らかにすることを目的とする。本年度の成果を要約する。 1)日本人に多い胃癌・肺癌・食道癌の腫瘍細胞株を樹立するとともに、腫瘍内浸潤リンパ球からIL〜2にて、自家癌特異的キラーT細胞株およびヘルパーT細胞株を樹立した。癌抗原ペプチドの提示分子が、自己MHC分子であるHLA-A31,HLA-A2601であることが証明された。さらに、HLA分子結合ペプチド画分の精製に成功した。 2)自家癌反抗性キラーT細胞株から、完全長のTCRα,TCRβ鎖cDNAクローンを単離し、シーケンスを決定、発現ベクターに組み込んだ。 3)癌化に伴い発現する糖鎖抗原や癌細胞表面に多量に発現する癌遺伝子産物(c-erbB2)に対し、宿主抗癌免疫活性を誘導する方法を開発した。以上により、人癌の免疫遺伝子治療に向けた癌抗原ペプチドの同定法や癌特異的免疫能の移入について知見の集積がなされ、今後の展開の基礎が確立された。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Yasoshima,T.,Kikuchi,K.他: "The mechanism of human autologous gastric signet ring cell tumor rejection by cytotoxic T lymphocytes in the possible context of ……" Cancer. 87. 411-446 (1995)
[Publications] Ueda,D.,Kikuchi,K.他: "T cell receptor gene structure of HLA-A-26-restricted cytotoxic T lymphocyte lines against human autologous pancreatic adenocarcinoma." Jpn.J.Cancer Res.86. 691-697 (1995)
[Publications] Shichijo,S.,Itoh,K.他: "Deterction of MAGE-4 protein on lung cancers." Int.J.Cancer. 64. 158-165 (1995)
[Publications] Shichijo,S.,Itoh,K.他: "Preferential expression of MAGE gene family on human lymphocytic leukemias." Cancer Immunol. Immunother.41. 95-103 (1995)
[Publications] Imai,Y.,Itoh,K.他: "Sequence analysis of the MAGE gene family encoding human tumor-rejection antigens." Gene. 160. 287-290 (1995)
[Publications] Nakao,M.,Itoh,K.他: "HLA A2601-restricted cytotoxic T lymphocytes recognizing a peptide antigen expressed on squamous cell carcinoma." Cancer Res. 55. 4248-4252 (1995)
[Publications] Yamashita,Y.,Kannagi,R.他: "Alteration in gastric mucin with malignant transformation:novel pathway of mucin synthesis." J.Natl.Cancer Inst.87. 411-446 (1995)
[Publications] Ye,C.,Kannagi,R.他: "Expression of E-selection on endothelial cells of small veins and proliferating vessels in human colorectal carcinoma." Int.J.Cancer. 61. 455-460 (1995)
[Publications] Suematsu,M.,Kannagi,R.他: "Impairment of selectin-mediated leukocyte adhesion to venular endothelium in spontaneously hypertensive rats." J.Clin.Invest.96. 2009-2016 (1995)
[Publications] Suzuki,S.,Masuko,T.他: "Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells.Biol.Pharm.Bull." Biol.Pharm.Bull. 18. 1279-1282 (1995)
[Publications] Suzuki,S.,Masuko,T.他: "Cytotoxicity of anti-c-erbB-2 imunoliposomes containing doxorubicin on human cancer cells." Brit.J.Cancer. 72. 663-668 (1995)
[Publications] Okumura,C.,Furukawa,K.他: "Induction of murine γ δ T cells cytotoxic for xenogeneic racells." J.Immunol.154. 1114-1123 (1995)
[Publications] Kasahara,M.他: "Mapping of acidic epididymal glycoprotein(Aeg)genes to mouse chromsome 17." Mammalin Genome. 6. 52-54 (1995)
[Publications] Noguchi,M.,Kasahara,M.他: "The MHC class I-like Zu-α2-glycoprotein gene maps to mouse chromosome 5." Immounogenetics. 42. 72-74 (1995)
[Publications] Beck,Y.,L,Aatz.他: "Polymorphismof human minor histocompatibility antigen:T cell recognition of human minor histocompatibility peptides presented・・・" JExp.Med.181. 2038-2048 (1995)
[Publications] Kandil,E.,Kasahara,M.他: "Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene." J.Immunol. 154. 5907-5918 (1995)
[Publications] Ikeda,H.,Matsuura,A.他: "Clonal dominance of human autologous cytotoxic Tlymphocytes against gastric carcinoma:Molecular stability of complimentarity determining region-3structure of T cell receptor α/β gene." Immunol.8. 75-82 (1996)
[Publications] Matsuura,A.,Itoh,Y.他: "Molecular cloning of the rat CD ζ/η/θgene." Transplantation Proc.27. 1512-1514 (1995)

1995 Fiscal Year Annual Research Report

ヒト自家癌拒絶の免疫学的分子機構

Principal Investigator

菊地 浩吉 札幌医科大学, 医学部, 教授 (00045345)

Research Products

[Publications] Yasoshima,T.,Kikuchi,K.他: "The mechanism of human autologous gastric signet ring cell tumor rejection by cytotoxic T lymphocytes in the possible context of ……" Cancer. 87. 411-446 (1995)

[Publications] Ueda,D.,Kikuchi,K.他: "T cell receptor gene structure of HLA-A-26-restricted cytotoxic T lymphocyte lines against human autologous pancreatic adenocarcinoma." Jpn.J.Cancer Res.86. 691-697 (1995)

[Publications] Shichijo,S.,Itoh,K.他: "Deterction of MAGE-4 protein on lung cancers." Int.J.Cancer. 64. 158-165 (1995)

[Publications] Shichijo,S.,Itoh,K.他: "Preferential expression of MAGE gene family on human lymphocytic leukemias." Cancer Immunol. Immunother.41. 95-103 (1995)

[Publications] Imai,Y.,Itoh,K.他: "Sequence analysis of the MAGE gene family encoding human tumor-rejection antigens." Gene. 160. 287-290 (1995)

[Publications] Nakao,M.,Itoh,K.他: "HLA A2601-restricted cytotoxic T lymphocytes recognizing a peptide antigen expressed on squamous cell carcinoma." Cancer Res. 55. 4248-4252 (1995)

[Publications] Yamashita,Y.,Kannagi,R.他: "Alteration in gastric mucin with malignant transformation:novel pathway of mucin synthesis." J.Natl.Cancer Inst.87. 411-446 (1995)

[Publications] Ye,C.,Kannagi,R.他: "Expression of E-selection on endothelial cells of small veins and proliferating vessels in human colorectal carcinoma." Int.J.Cancer. 61. 455-460 (1995)

[Publications] Suematsu,M.,Kannagi,R.他: "Impairment of selectin-mediated leukocyte adhesion to venular endothelium in spontaneously hypertensive rats." J.Clin.Invest.96. 2009-2016 (1995)

[Publications] Suzuki,S.,Masuko,T.他: "Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells.Biol.Pharm.Bull." Biol.Pharm.Bull. 18. 1279-1282 (1995)

[Publications] Suzuki,S.,Masuko,T.他: "Cytotoxicity of anti-c-erbB-2 imunoliposomes containing doxorubicin on human cancer cells." Brit.J.Cancer. 72. 663-668 (1995)

[Publications] Okumura,C.,Furukawa,K.他: "Induction of murine γ δ T cells cytotoxic for xenogeneic racells." J.Immunol.154. 1114-1123 (1995)

[Publications] Kasahara,M.他: "Mapping of acidic epididymal glycoprotein(Aeg)genes to mouse chromsome 17." Mammalin Genome. 6. 52-54 (1995)

[Publications] Noguchi,M.,Kasahara,M.他: "The MHC class I-like Zu-α2-glycoprotein gene maps to mouse chromosome 5." Immounogenetics. 42. 72-74 (1995)

[Publications] Beck,Y.,L,Aatz.他: "Polymorphismof human minor histocompatibility antigen:T cell recognition of human minor histocompatibility peptides presented・・・" JExp.Med.181. 2038-2048 (1995)

[Publications] Kandil,E.,Kasahara,M.他: "Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene." J.Immunol. 154. 5907-5918 (1995)

[Publications] Ikeda,H.,Matsuura,A.他: "Clonal dominance of human autologous cytotoxic Tlymphocytes against gastric carcinoma:Molecular stability of complimentarity determining region-3structure of T cell receptor α/β gene." Immunol.8. 75-82 (1996)

[Publications] Matsuura,A.,Itoh,Y.他: "Molecular cloning of the rat CD ζ/η/θgene." Transplantation Proc.27. 1512-1514 (1995)

菊地浩吉札幌医科大学, 医学部, 教授 (00045345)