2001 Fiscal Year Annual Research Report

ヒトCD8+キラーT細胞による認識されるがん拒絶抗原の解析

Research Project

Project/Area Number	12213134
Research Institution	Kurume University
Principal Investigator	伊東恭悟久留米大学, 医学部, 教授 (50125499)
Keywords	遺伝子 / 拒絶抗原 / ペプチド / 免疫 / キラーT細胞 / ワクチン / 探索的臨床研究 / テーラーメイド型医療
Research Abstract	キラーT細胞により認識されるヒト上皮性がん拒絶抗原遺伝子のクローニングとペプチド抗原の同定の研究にて、HLA-A24拘束性分子としては転移癌に発現するLck分子(Harashima et al.,Eur.J.Immunol,31:323)や薬剤耐性に関与するMDR3を同定した(Yamada et al.,Can.Res.,61:6458)、またHLA-A2拘束性分子の同定においては本年度は多くの成果を得た。即ち、膵臓癌由来6つの分子と12ペプチド(Ito, et al., Can. Res. 61:2038)、Lck及びCypB由来HLA-A2結合性ペプチドの同定である。これらのペプチドでは第1相/第2相臨床試験に使用中である。更に大腸癌由来cDNAより45個の分子と133ペプチドを同定した。またHLA-B46,-B52拘束性分子とペプチドを世界ではじめて同定した。一方、初期のペプチドワクチン第1相臨床試験にてその安全性と特異免疫誘導能を確認した(Miyagi et al.,Clin.Can.Res.,7:3950)。患者個々のCTL前駆体を同定してのテーラーメイド型レジメにて2000年10月より開始し、2002年1月末現在にて評価可能な62症例にて安全性を確認、かつ特異免疫誘導能は、ほぼ全例で確認された。臨床効果は3ケ月評価でPR2,SD30,PD30であり、何らかの抗腫瘍作用は62例中27例(44%)に及んだ。さらに、384wellを用いたペプチド特異的CTL同定法を確立した。これらの研究結果は、がん患者個々の免疫学的特性(HLA 多様性、がん抗原の有無、CTL前駆体や抗体の有無)に基づいたテーラーメイド型がん予防や治療法の開発に科学的基盤を賦与するものと考えられる。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Nakatsura, R: "Cellular and humoral immune responses to a human pancreatic cancer antigen, CLP, originally defined by the SEREX method"Eur. J. Immunology. (in press). (2002)
[Publications] Miyagi, Y: "Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination of SART3 peptides"Clin. Can. Res.. 7. 3950-3962 (2001)
[Publications] Suzuki, N.: "Detection of peptide-specific Cytotoxic T lymphocyte precursors used for specific immunotherapy of pancreatic cancer"Int. J. Cancer. (in press). (2001)
[Publications] Yamada, A.: "Multidrug resistance-associated protein 3 is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Res.. 61. 6459-6466 (2001)
[Publications] Imai, N.: "Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases"Int. J. Cancer. 94. 237-242 (2001)
[Publications] Inoue, Y: "Induction of tumor specific cytotoxic T lymphocytes in prostate cancer using prostatic acid phosphatase derived HLA-A2402 binding peptide"J. Urol.. 166. 1508-1513 (2001)
[Publications] Harada, K.: "Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing activation factor RNPS1 : a possible regulation of splicing by a complex formation"Int. J. Cancer. 93. 623-629 (2001)
[Publications] Ito, M.: "Molecular basis of T cell-mediated recognition of pancreatic cancer cells"Cancer Res.. 61. 2038-2046 (2001)
[Publications] Suefuji, Y.: "Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients"British J. Cancer. 84. 915-919 (2001)
[Publications] Harashima, N.: "Recognition of the Lck tyrosine kinase as a tumor antigen by T cells of metastatic cancer patients"Eur. J. Immunology. 31. 323-332 (2001)
[Publications] Kyogo Itoh: "Tumor Immunology Series volume III"Drs. Kawakami and Parmiani (harwood academic publishers)(in press). (2002)

2001 Fiscal Year Annual Research Report

ヒトCD8+キラーT細胞による認識されるがん拒絶抗原の解析

Principal Investigator

伊東 恭悟 久留米大学, 医学部, 教授 (50125499)

Research Products

[Publications] Nakatsura, R: "Cellular and humoral immune responses to a human pancreatic cancer antigen, CLP, originally defined by the SEREX method"Eur. J. Immunology. (in press). (2002)

[Publications] Miyagi, Y: "Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination of SART3 peptides"Clin. Can. Res.. 7. 3950-3962 (2001)

[Publications] Suzuki, N.: "Detection of peptide-specific Cytotoxic T lymphocyte precursors used for specific immunotherapy of pancreatic cancer"Int. J. Cancer. (in press). (2001)

[Publications] Yamada, A.: "Multidrug resistance-associated protein 3 is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Res.. 61. 6459-6466 (2001)

[Publications] Imai, N.: "Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases"Int. J. Cancer. 94. 237-242 (2001)

[Publications] Inoue, Y: "Induction of tumor specific cytotoxic T lymphocytes in prostate cancer using prostatic acid phosphatase derived HLA-A2402 binding peptide"J. Urol.. 166. 1508-1513 (2001)

[Publications] Harada, K.: "Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing activation factor RNPS1 : a possible regulation of splicing by a complex formation"Int. J. Cancer. 93. 623-629 (2001)

[Publications] Ito, M.: "Molecular basis of T cell-mediated recognition of pancreatic cancer cells"Cancer Res.. 61. 2038-2046 (2001)

[Publications] Suefuji, Y.: "Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in breast cancer patients"British J. Cancer. 84. 915-919 (2001)

[Publications] Harashima, N.: "Recognition of the Lck tyrosine kinase as a tumor antigen by T cells of metastatic cancer patients"Eur. J. Immunology. 31. 323-332 (2001)

[Publications] Kyogo Itoh: "Tumor Immunology Series volume III"Drs. Kawakami and Parmiani (harwood academic publishers)(in press). (2002)

伊東恭悟久留米大学, 医学部, 教授 (50125499)