1994 年度実績報告書

ヒト自家癌拒絶の免疫学的分子機構

研究課題

研究課題/領域番号	06282117
研究機関	札幌医科大学
研究代表者	菊地浩吉札幌医科大学, 医学部, 教授 (00045345)
研究分担者	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) 笠原正典北海道大学, 医学部, 助教授 (30241318) 神奈木玲児愛知県がんセンター, 部長 (80161389) 伊東恭悟久留米大学, 医学部, 教授 (50125499)
キーワード	腫瘍免疫 / 癌抗原ペプチド / HLA / 癌遺伝子 / クラスIb / T細胞レセプター
研究概要	癌は遺伝子の病気であり、遺伝子変異に伴い細胞増殖や生存に有利な形質を獲得するとともに腫瘍抗原を発現するに到る。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・食堂癌の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。抗HLA抗体による阻害活性から、癌抗原ペプチドの提示分子が、自己MHC分子であるHLA-A31,HLA-12601であることが証明された。さらに、酸処理によるHLA分子結合ペプチド画分の精製に成功した。 2)自家癌反応性キラーT細胞株のT細胞レセプターusageを検討し、TCRα,TCRβ鎖cDNAクローンを単離し、一次構造を決定した。 3)癌細胞表面に多量に発現する癌遺伝子産物(c-erbB2)や癌化に伴い発現する糖鎖抗原に対し、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の知見の集積がなされ、今後の展開の基礎が確立された。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Yasoshima,T.,Kikuchi,K.他: "The mechanism of human autologous gastric signet ring cell tumor rejection by cytotoxic T lylmphocytes in the possible context of・・・" Cancer. (in press).
[文献書誌] Qi,W.,Kikuchi,K.他: "Transformation-associated 86kDa natural killer target molecule expressed on the mouse,rat and human cell surface" J.J.Cancer Res. 85. 862-868 (1994)
[文献書誌] Murray,jL.,Itoh.K.他: "Phase I trial of murine monoclonal antibody 14G2a aministered by prolonged intravenous infusion in patients with neuroectodermal・・・・・" J.Clin.Onocology. 12. 184-193 (1994)
[文献書誌] Khakevitch,DD.,Itoh,K.他: "Characterzation of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic・・・・・・" Int.J.Cancer. 53. 317-323 (1994)
[文献書誌] Seito,E.,Ithoh,K.他: "Polyclonal usage of T-cell receptor (TCR)α and β genes for cytotoxic T lymphocytes in human metastatic melanoma;poddible involvement・・・・・" Int.J.Cancer. 58. 497-502 (1994)
[文献書誌] Imai,Y.,Itoh,K.: "Sequence analysis of the MAGE gene family encoding human tumorrejection antigens." Gene. (in press). (1995)
[文献書誌] Yamashita,Y.,Kannagi,R.他: "A newcancer-associated antigen difined by a monoclonal antibody against a svnthetic carbohydrate antigen." Int.J.Cancer. 58. 349-355 (1994)
[文献書誌] Furukawa,Y.,Kannagi,R.他: "Variant type of sialy Lewis X antigen expressed on adult T cell leukemia cells is associated with skin involvement." Cancer Ress.54. 6533-6538
[文献書誌] Natsuka,S.,Kannagi,R.他: "Molecular cloning if a cDNA encoding a novel human leukocyte α-1,3-fucosyltrans ferase capableofsynthesizing the sialyl Lewis・・・・・・・・" J.Biol.Chem.269. 16789-16794 (1994)
[文献書誌] Ueno,H.,Masuko,T.他: "Epitope mapping of bovine serum albumin using monoclonal antibodies coupled with a photoreactive crosslinker." J.Biochem.115. 1119-1127 (1994)
[文献書誌] Suzuki,S.,Masuko.T.他: "Endocytosis does not necessarily augment the cytotoxicity of adriamycin encapsuledin immunoliposomes." Biochim.Bophys.Acta. 1224. 445-453 (1994)
[文献書誌] Furukawa,K.,Mori,M.他: "Clonal Expansion of CD8^+ cytotoxic T lymphocytes against human T cell lymphotropic virustypeI(HTLV-I)genome prducts in HTLV-・・・・・・・・・" J.Clin.Inv.94. 1830-1839 (1994)
[文献書誌] Yang,H.,Furukawa,K.他: "Oligoclonal expansionof CD8^+ T lymphocytes in cultured peripheral lymphocytes derivd from asymptomatic HTLV-I carriers." Int.J.Oncol.5/2. 159-167 (1994)
[文献書誌] Salter-Cid,L.,Kasahara,M.他: "Hsp70 genes are linked to the zenopus major histocompatibility complex" Immunogenetics. 39. 1-7
[文献書誌] Beck,Y.,L,Satz.他: "Polymorphismof human minor histocompatibility antigen:T cell recognition ofhumanminor histocompatibility peptides presented・・・・" JExp.Med.(in press).
[文献書誌] Ichimiya,S.,Matsuura,A.他: "Structural analysis of the rat homologuof CD1:Evidence for evolutionary conservation of the CD1D class and widespread・・・・・・・・・" J.Immunol.153. 1112-1123 (1994)
[文献書誌] Kinebuhci,M.,Matsuura,A.他: "Rat T-cell receptor γ chain seqences: Identification of conserved gene segments and unique chimeric constant region gene,C4L." Immunogentetics. 40. 449-455 (1994)
[文献書誌] Matsuura,A.,Itoh,Y.他: "Molecular cloning of the rat CD ζ/η/θ gene." Transplantation Proc.27. 1512-1514 (1995)

1994 年度 実績報告書

ヒト自家癌拒絶の免疫学的分子機構

研究代表者

菊地 浩吉 札幌医科大学, 医学部, 教授 (00045345)

研究成果

[文献書誌] Yasoshima,T.,Kikuchi,K.他: "The mechanism of human autologous gastric signet ring cell tumor rejection by cytotoxic T lylmphocytes in the possible context of・・・" Cancer. (in press).

[文献書誌] Qi,W.,Kikuchi,K.他: "Transformation-associated 86kDa natural killer target molecule expressed on the mouse,rat and human cell surface" J.J.Cancer Res. 85. 862-868 (1994)

[文献書誌] Murray,jL.,Itoh.K.他: "Phase I trial of murine monoclonal antibody 14G2a aministered by prolonged intravenous infusion in patients with neuroectodermal・・・・・" J.Clin.Onocology. 12. 184-193 (1994)

[文献書誌] Khakevitch,DD.,Itoh,K.他: "Characterzation of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic・・・・・・" Int.J.Cancer. 53. 317-323 (1994)

[文献書誌] Seito,E.,Ithoh,K.他: "Polyclonal usage of T-cell receptor (TCR)α and β genes for cytotoxic T lymphocytes in human metastatic melanoma;poddible involvement・・・・・" Int.J.Cancer. 58. 497-502 (1994)

[文献書誌] Imai,Y.,Itoh,K.: "Sequence analysis of the MAGE gene family encoding human tumorrejection antigens." Gene. (in press). (1995)

[文献書誌] Yamashita,Y.,Kannagi,R.他: "A newcancer-associated antigen difined by a monoclonal antibody against a svnthetic carbohydrate antigen." Int.J.Cancer. 58. 349-355 (1994)

[文献書誌] Furukawa,Y.,Kannagi,R.他: "Variant type of sialy Lewis X antigen expressed on adult T cell leukemia cells is associated with skin involvement." Cancer Ress.54. 6533-6538

[文献書誌] Natsuka,S.,Kannagi,R.他: "Molecular cloning if a cDNA encoding a novel human leukocyte α-1,3-fucosyltrans ferase capableofsynthesizing the sialyl Lewis・・・・・・・・" J.Biol.Chem.269. 16789-16794 (1994)

[文献書誌] Ueno,H.,Masuko,T.他: "Epitope mapping of bovine serum albumin using monoclonal antibodies coupled with a photoreactive crosslinker." J.Biochem.115. 1119-1127 (1994)

[文献書誌] Suzuki,S.,Masuko.T.他: "Endocytosis does not necessarily augment the cytotoxicity of adriamycin encapsuledin immunoliposomes." Biochim.Bophys.Acta. 1224. 445-453 (1994)

[文献書誌] Furukawa,K.,Mori,M.他: "Clonal Expansion of CD8^+ cytotoxic T lymphocytes against human T cell lymphotropic virustypeI(HTLV-I)genome prducts in HTLV-・・・・・・・・・" J.Clin.Inv.94. 1830-1839 (1994)

[文献書誌] Yang,H.,Furukawa,K.他: "Oligoclonal expansionof CD8^+ T lymphocytes in cultured peripheral lymphocytes derivd from asymptomatic HTLV-I carriers." Int.J.Oncol.5/2. 159-167 (1994)

[文献書誌] Salter-Cid,L.,Kasahara,M.他: "Hsp70 genes are linked to the zenopus major histocompatibility complex" Immunogenetics. 39. 1-7

[文献書誌] Beck,Y.,L,Satz.他: "Polymorphismof human minor histocompatibility antigen:T cell recognition ofhumanminor histocompatibility peptides presented・・・・" JExp.Med.(in press).

[文献書誌] Ichimiya,S.,Matsuura,A.他: "Structural analysis of the rat homologuof CD1:Evidence for evolutionary conservation of the CD1D class and widespread・・・・・・・・・" J.Immunol.153. 1112-1123 (1994)

[文献書誌] Kinebuhci,M.,Matsuura,A.他: "Rat T-cell receptor γ chain seqences: Identification of conserved gene segments and unique chimeric constant region gene,C4L." Immunogentetics. 40. 449-455 (1994)

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

1994 年度実績報告書

菊地浩吉札幌医科大学, 医学部, 教授 (00045345)