Development of cancer immunotherapy using co-transfer of cancer-specific TCR gene and chemokine receptor gene

• Project/Area Number: 21390294
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: YASUKAWA Masaki 愛媛大学, 大学院・医学系研究科, 教授 (60127917)
• Co-Investigator(Renkei-kenkyūsha): HASEGAWA Hitoshi 愛媛大学, 大学院・医学系研究科, 准教授 (40164826) ; FUJIWARA Hiroshi 愛媛大学, 医学部附属病院, 講師 (20398291)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: がん免疫療法 / T細胞レセプター遺伝子 / ケモカイン・ケモカインレセプター / WT1 / Aurora-A kinase / 白血病 / 肺がん / WTI / 遺伝子治療 / 細胞傷害性T細胞 / T細胞レセプター / ケモカイン / ヒト化マウス / がん免疫 / レトロウイルスベクター

Research Abstract

In order to develop a novel cancer immunotherapy, we verified the efficacy and safety of adoptive transfer using cytotoxic T lymphocytes(CTLs) transduced with cancer-specific T-cell receptor(TCR) gene and receptor gene for chemokine which is abundantly produced in cancer microenvironment. Our data demonstrate that adoptive transfer of artificial CTLs expressing both cancer-specific TCR and chemokine receptor is more effective and safe than that of CTLs expressing only cancer-specific TCR.

Research Products

• [Journal Article] The role of activation-induced cytidine deaminase(AID/AICDA) in the progression of follicular lymphoma (2012)
  • Author(s): Shikata, H. Yasukawa, M., 他8名
  • Journal Title: Cancer Sci Volume: 103 Pages: 415-421
  • Peer Reviewed
• [Journal Article] Aurora kinase A-specific T-cell receptor gene transfer redirects T-lymphocytes to display effective anti-leukemia reactivity (2012)
  • Author(s): Nagai, K., Fujiwara, H., Yasukawa, M., 他9名
  • Journal Title: Blood Volume: 119 Pages: 368-376
  • Peer Reviewed
• [Journal Article] The role of activation-induced cytidine deaminase (AID/AICDA) in the progression of follicular lymphoma (2012)
  • Author(s): Shikata H, Yasukawa M, et al
  • Journal Title: Cancer Sci Volume: 103 Issue: 3 Pages: 415-421
  • DOI: 10.1111/j.1349-7006.2011.02186.x
  • Peer Reviewed
• [Journal Article] Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-βproduction (2011)
  • Author(s): Hasegawa, H. Yasukawa, M., 他4名
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 526-531
  • Peer Reviewed
• [Journal Article] Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked anti-leukemia reactivity and safety (2011)
  • Author(s): Ochi, T., Fujiwara, H., Yasukawa, M., 他7名
  • Journal Title: Blood Volume: 118 Pages: 1495-1503
  • Peer Reviewed
• [Journal Article] Adoptive T-cell immunotherapy using T-cell receptor gene transfer : aiming at a cure for cancer (2011)
  • Author(s): Yasukawa, M. Fujiwara, H., 他1名
  • Journal Title: Immunotherapy Volume: 3 Pages: 135-140
  • Peer Reviewed
• [Journal Article] Feasibility of gene-immunotherapy using WT1-specific T-cell receptor gene transfer for infant acute lymphoblastic leukemia with MLL gene rearrangement (2011)
  • Author(s): Nagai, K., Fujiwara, H., Yasukawa, M., 他7名
  • Journal Title: Blood Cancer J Volume: 1 Pages: 10-10
  • Peer Reviewed
• [Journal Article] Requisite considerations for successful adoptive immunotherapy with engineered T lymphocytes using tumor antigen-specific T-cell receptor gene transfer (2011)
  • Author(s): Ochi, T., Fujiwara, H. and Yasukawa, M.
  • Journal Title: Expert Opin. Biol. Ther. Volume: 11 Pages: 699-713
  • Peer Reviewed
• [Journal Article] Gemcitabine enhances Wilms' tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune response (2011)
  • Author(s): Takahara, A., Fujiwara, H., Yasukawa, M., 他13名
  • Journal Title: Cancer Immunol. Immunother. Volume: 60 Pages: 1289-1297
  • Peer Reviewed
• [Journal Article] FDG-PET can evaluate the treatment for fungal liver abscess much earlier than other imagings (2011)
  • Author(s): Miyazaki, Yasukawa, M., 他7名
  • Journal Title: Ann. Hematol
  • Peer Reviewed
• [Journal Article] Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis (2011)
  • Author(s): An, J., Fujiwara, H., Yasukawa, M., 他10名
  • Journal Title: Int. J. Hemattol Volume: 93 Pages: 176-185
  • NAID: 10029533085
  • Peer Reviewed
• [Journal Article] Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-ss production (2011)
  • Author(s): Hasegawa H, Yasukawa M, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 526-531
  • Peer Reviewed
• [Journal Article] Gemcitabine enhances Wilms' tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune response (2011)
  • Author(s): Takahara A, Yasukawa M, et al
  • Journal Title: Cancer Immunol.Immunother. Volume: 60 Pages: 1289-1297
  • Peer Reviewed
• [Journal Article] Feasibility of gene-immunotherapy using WT1-specific T-cell receptor gene transfer for infant acute lymphoblastic leukemia with MLL gene rearrangement (2011)
  • Author(s): Nagai K, Yasukawa M, et al
  • Journal Title: Blood Cancer J Volume: 1
  • Peer Reviewed
• [Journal Article] Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis (2011)
  • Author(s): An J, Yasukawa M, et al
  • Journal Title: Int.J.Hemattol. Volume: 93 Pages: 176-185
  • NAID: 10029533085
  • Peer Reviewed
• [Journal Article] Requisite considerations for successful adoptive immunotherapy with engineered T lymphocytes using tumor antigen-specific T-cell receptor genetransfer (2011)
  • Author(s): Ochi, T., Fujiwara, H., Yasukawa M.
  • Journal Title: Expert Opin.Biol.Ther. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Feasibility of gene-immunotherapy using WT1-specific T-cell receptor gene transfer for infant acute lymphoblastic leukemia with MLL gene rearrangement (2011)
  • Author(s): Nagai, K., Yasukawa, M., et al.
  • Journal Title: Blood Cancer J Volume: 1
  • Peer Reviewed
• [Journal Article] Vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay for platelet response to cilostazol (2011)
  • Author(s): Yamanouchi, J., Yasukawa, M., et al.
  • Journal Title: Platelets Volume: 22 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator^-activated receptorαandγagonists together with TGF-βconvert human CD4^+ CD25^-T cells into functional Foxp3^+ regulatory T cells (2010)
  • Author(s): Lei, J., Hasegawa, H., Yasukawa, M., 他2名
  • Journal Title: J. Immunol Volume: 185 Pages: 7186-7198
  • Peer Reviewed
• [Journal Article] Generation of functional human T cells with HLA-restricted immune responses in HLA-class I expressing NOD/SCID/IL2rγ^<null> humanized mice (2010)
  • Author(s): Shultz, L., Fujiwara, H., Yasukawa, M., 他9名
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 13022-13027
  • Peer Reviewed
• [Journal Article] Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes (2010)
  • Author(s): Nagai, K., Fujiwara, H., Yasukawa, M., 他9名
  • Journal Title: PLoS One Volume: 5 Pages: 14173-14173
  • Peer Reviewed
• [Journal Article] HLA class I binding of HBZ determines outcome in HTLV-1 infection (2010)
  • Author(s): MacNamara, A., Fujiwara, H., Yasukawa, M., 他7名
  • Journal Title: PLoS Pathog Volume: 6 Pages: 1001117-1001117
  • Peer Reviewed
• [Journal Article] Allo-HLA reactivity of leukemia-specific cytotoxic T lymphocytes. e-Letter (2010)
  • Author(s): Yasukawa, M. Fujiwara, H., 他5名
  • Journal Title: Blood Accessed April Volume: 19
  • Peer Reviewed
• [Journal Article] Relapse of renal cell carcinoma with disappearance of HLA class I following hTERT peptide vaccination (2010)
  • Author(s): Yasukawa, M. Fujiwara, H., 他2名
  • Journal Title: Ann. Oncol Volume: 21 Pages: 2122-2124
  • Peer Reviewed
• [Journal Article] Derivative(1 ; 18)(q10 ; q10) in essential thrombocythemia (2010)
  • Author(s): Azuma, T., Fujiwara, H., Yasukawa M., 他6名
  • Journal Title: Cancer Genet. Cytogenet Volume: 199 Pages: 62-64
  • Peer Reviewed
• [Journal Article] Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR (2010)
  • Author(s): Okamoto, S, Fujiwara, H., Yasukawa, M., 他4名
  • Journal Title: Cancer Res Volume: 69 Pages: 9003-9011
  • Peer Reviewed
• [Journal Article] HLA class I binding of HBZ determines outcome in HTLV-1 infection (2010)
  • Author(s): MacNamara, A., Yasukawa, M., et al.
  • Journal Title: PLoS Pathog. Volume: 6
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor α and γ agonists together with TGF-β convert human CD4+CD25- T cells into functional Foxp3^+ regulatory T cells (2010)
  • Author(s): Lei, J., Yasukawa, M., et al.
  • Journal Title: J.Immunol. Volume: 185 Pages: 7186-7198
  • Peer Reviewed
• [Journal Article] Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes (2010)
  • Author(s): Nagai, K., Yasukawa, M., et al.
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] Relapse of renal cell carcinoma with disappearance of HLA class I following hTERT peptide vaccination (2010)
  • Author(s): Yasukawa, M., Ochi, T., Fujiwara, H.
  • Journal Title: Ann.Oncol. Volume: 21 Pages: 2122-2124
  • Peer Reviewed
• [Journal Article] Generation of functional human T cells with HLA-restricted immune responses in HLA-class I expressing NOD/SCID/IL2rγ^<null> humanized mice (2010)
  • Author(s): Shultz, L., Yasukawa, M., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 107 Pages: 13022-13027
  • Peer Reviewed
• [Journal Article] Application of adoptive T-cell therapy using tumor antigen-specific T-cell receptor gene transfer for the treatment of human leukemia (2010)
  • Author(s): Ochi T, Yasukawa M, et al.
  • Journal Title: J.Biomed.Biotech. (In press)
  • Peer Reviewed
• [Journal Article] Aurora-A kinase : A novel target of cellular immunotherapy for leukemia (2009)
  • Author(s): Ochi, T., Fujiwara, H., Yasukawa, M., 他5名
  • Journal Title: Blood Volume: 113 Pages: 66-74
  • Peer Reviewed
• [Journal Article] The role of zinc finger protein 521/early hematopoietic zinc finger protein in erythroid cell differentiation (2009)
  • Author(s): Matsubara, E., Yasukawa, M., 他6名
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 3480-3487
  • Peer Reviewed
• [Journal Article] HBZ is an immunogenic protein but not a target antigen for HTLV-1-specific cytotoxic T lymphocytes (2009)
  • Author(s): Suemori, K., Fujiwara, H., Yasukawa, M., 他5名
  • Journal Title: J. Gen. Virol Volume: 90 Pages: 1806-1811
  • Peer Reviewed
• [Journal Article] Identification of a novel epitope derived from CML66 which is recognized by anti-leukaemia cytotoxic T lymphocytes (2009)
  • Author(s): Suemori, K., Fujiwara, H., Yasukawa, M., 他6名
  • Journal Title: Br. J. Haematol Volume: 146 Pages: 115-118
  • Peer Reviewed
• [Journal Article] Clinical efficacy of WT1 peptide vaccination in patients with acute myelogenous leukemia and myelodysplastic syndrome (2009)
  • Author(s): Yasukawa, M. Fujiwara, H., 他5名
  • Journal Title: Am. J. Hematol Volume: 84 Pages: 314-315
  • Peer Reviewed
• [Journal Article] Aurora-A kinase : A novel target of cellular immunotherapy for leukemia (2009)
  • Author(s): Ochi T, Yasukawa M, et al.
  • Journal Title: Blood 113 Pages: 66-74
  • Peer Reviewed
• [Journal Article] The role of zinc finger protein 521/early hematopoietic zinc finger protein in erythroid cell differentiation (2009)
  • Author(s): Matsubara E, Yasukawa M, et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 3480-3487
  • Peer Reviewed
• [Journal Article] Clinical efficacy of WT1 peptide vaccination in patients with acute myelogenous leukemia and myelodysplastic syndrome (2009)
  • Author(s): Yasukawa M, et al.
  • Journal Title: Am.J.Hematol. 84 Pages: 314-315
  • Peer Reviewed
• [Journal Article] Identification of a novel epitope derived from CML66 which is recognized by anti-leukaemia cytotoxic T lymphocytes (2009)
  • Author(s): Suemori K, Yasukawa M, et al
  • Journal Title: Br.J.Haematol 146 Pages: 115-118
  • Peer Reviewed
• [Journal Article] HBZ is an immunogenic protein but not a target antigen for HTLV-1-specific cytotoxic T lymphocytes (2009)
  • Author(s): Suemori K, Yasukawa M, et al
  • Journal Title: J.Gen.Virol. 90 Pages: 1806-1811
  • Peer Reviewed
• [Journal Article] Aurora-A kinase : a novel target both for cellular immunotherapy and molecular target therapy against human leukemia (2009)
  • Author(s): Ochi T, Yasukawa M, et al.
  • Journal Title: Expert Opin. Ther.Targets 13 Pages: 1399-1410
  • Peer Reviewed
• [Journal Article] Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR (2009)
  • Author(s): Okamoto S, Yasukawa M, et al
  • Journal Title: Cancer Res. 69 Pages: 9003-9011
  • Peer Reviewed
• [Presentation] Human Telomerase Reverse Transcriptase-Specific T-Cell Receptor Gene Transfer Redirects T-Lymphocytes to Exert Effective Antitumor Reactivity Against Adult T-Cell Leukemia. (2011)
  • Author(s): Miyazaki Y, Yasukawa M, et al
  • Organizer: 53^<rd> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego, U. S. A
  • Year and Date: 2011-12-12
• [Presentation] Redirected CD4^+ T Cells Using WT1-Specific T-Cell Receptor Gene Transfer Can Supply Multifactorial Help to Enhance the Anti-Leukemia Reactivity Mediated by Similarly Redirected CD8^+ T Cells Using the Identical Gene Transfer (2011)
  • Author(s): Ochi T, Yasukawa M, et al
  • Organizer: 53^<rd> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego, U. S. A
  • Year and Date: 2011-12-12
• [Presentation] Human Telomerase Reverse Transcriptase-Specific T-Cell Receptor Gene Transfer Redirects T-Lymphocytes to Exert Effective Antitumor Reactivity Against Adult T-Cell Leukemia (2011)
  • Author(s): Miyazaki Y, Yasukawa M, et al
  • Organizer: 53^<rd> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2011-12-12
• [Presentation] Redirected CD4+ T Cells Using WT1-Specific T-Cell Receptor Gene Transfer Can Supply Multifactorial Help to Enhance the Anti-Leukemia Reactivity Mediated by Similarly Redirected CD8+ T Cells Using the Identical Gene Transfer (2011)
  • Author(s): Ochi T, Yasukawa M, et al
  • Organizer: 53^<rd> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2011-12-12
• [Presentation] Forced Expression of CC Chemokine Receptor 2 Enhances Anti-Cancer Reactivity Mediated by T Lymphocytes Beforehand Redirected Toward WT1 Inside the Tumor Microenvironment (2011)
  • Author(s): Asai A, Yasukawa M, et al
  • Organizer: 53^<rd> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego, U. S. A
  • Year and Date: 2011-12-10
• [Presentation] Forced Expression of CC Chemokine Receptor 2 Enhances Anti-Cancer Reactivity Mediated by T Lymphocytes Beforehand Redirected Toward WT1 Inside the Tumor Microenvironment (2011)
  • Author(s): Asai A, Yasukawa M, et al
  • Organizer: 53^<rd> Annual Meeting of American Society of Hematology
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2011-12-10
• [Presentation] Augmented Expression of WT1-Specific TCR and Inhibition of Mispaired-TCR Formation In TCR-Gene Modified T-Cells Can Concomitantly Be Achieved Using a Novel Retroviral Vector with Silencers for Endogenous TCRs (2010)
  • Author(s): Ochi, T., Yasukawa, M., et al.
  • Organizer: American Society of Hematology 52^<nd> Annual Meeting
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2010-12-13
• [Presentation] Engineering of Human T-Cells with a Novel Aurora-A Kinase-Specific T-Cell Receptor Gene Transfer Confers Anti-Leukemia Reactivity (2010)
  • Author(s): Nagai, K., Yasukawa, M., et al.
  • Organizer: American Society of Hematology 52^<nd> Annual Meeting
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2010-12-12
• [Presentation] Dual Engineering of Human CD8^+ T-Cells with WT1-Specific TCR Gene and Chemokine Receptor Gene Transfer Confers Functionally Strengthened Anti-Cancer Reactivity (2010)
  • Author(s): Miyazaki, Y., Yasukawa, M., et al.
  • Organizer: American Society of Hematology 52^<nd> Annual Meeting
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2010-12-12
• [Presentation] ウイルス感染とアレルギー (2009)
  • Author(s): 安川正貴
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-31
• [Presentation] HHV-6感染症-薬剤性過敏症症候群を中心として- (2009)
  • Author(s): 安川正貴
  • Organizer: 第83回日本感染症学会総会・学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-23
• [Book] 「造血器腫瘍に対する細胞免疫療法」Annual Review血液2012 (2012)
  • Author(s): 安川正貴
  • Publisher: 中外医学社
• [Book] 「免疫療法」造血器腫瘍学 (2012)
  • Author(s): 安川正貴
  • Publisher: 日本臨床社
• [Book] みんなに役立つ悪性リンパ腫の基礎と臨床 改訂版 (2011)
  • Author(s): 安川正貴
  • Total Pages: 538
  • Publisher: 医薬ジャーナル社
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.med1/
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.med1/
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.medl/contents/?cat=9
• [Remarks]
  • URL: http://www.m.ehime-u.ac.jp/school/int.med1/index.htm
• [Patent(Industrial Property Rights)] T細胞レセプター及び当該レセプターをコードする核酸 (2009)
  • Inventor(s): 安川正貴、他4名
  • Industrial Property Rights Holder: 安川正貴、愛媛大学、タカラバイオ株式会社
  • Filing Date: 2009-04-03
  • Overseas