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Development of novel treatment strategy against Hodgkin lymphoma based on the immunopathogenesis

Research Project

Project/Area Number 19390266
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNagoya City University

Principal Investigator

UEDA Ryuzo  Nagoya City University, 大学院・医学研究科, 教授 (20142169)

Co-Investigator(Kenkyū-buntansha) KOMATSU Hirokazu  名古屋市立大学, 大学院・医学研究科, 准教授 (60336675)
ISHIDA Takashi  名古屋市立大学, 大学院・医学研究科, 講師 (80405183)
INAGAKI Hiroshi  名古屋市立大学, 大学院・医学研究科, 教授 (30232507)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2008: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2007: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywordsホジキンリンパ腫 / 腫瘍免疫 / CCR4 / EBウィルス / MUM1 / IRF-4 / EBウイルス
Research Abstract

We have demonstrated that the anti-CCR4 mAb reduces the number of Treg cells among TIL in an in vivo NOG mouse model (bearing human tumor & engrafted with human immune cells). These results indicate that use of anti-CCR4 mAb could represent a novel strategy for the treatment not only of Hodgkin lymphoma, but also many other types of cancer by overcoming suppressive effects of Treg cells on the host's immune response to tumor cells. In the near future, the efficacy of the anti-CCR4 mAb in the latter context will also be established in clinical trials in humans.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (46 results)

All 2010 2009 2008 2007

All Journal Article (43 results) (of which Peer Reviewed: 43 results) Presentation (3 results)

  • [Journal Article] Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma (ATLL).2010

    • Author(s)
      Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, Iida S, Imada K, Uchiyama T, Akinaga S, Shitara K, Ueda R.
    • Journal Title

      Clin Cancer Res. 16

      Pages: 1520-1531

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients with Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma.2010

    • Author(s)
      Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y. Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R.
    • Journal Title

      J Clin Oncol. 28

      Pages: 1591-8

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phase I study of KW-0761, a defucosylated anit-CCR4 antibody, in relapsed patients with adult T-cell leukemia lymphoma and peripheral T-cell lymphoma2010

    • Author(s)
      Yamamoto K
    • Journal Title

      J Clin Oncol. 28(9)

      Pages: 1591-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma2010

    • Author(s)
      Ishii T
    • Journal Title

      Clin Cancer Res 16(5)

      Pages: 1520-1531

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary ATLL Cells mediated by autologous human immune cells in NOD/Shi-scid, IL-2Rgamma(null) mice in vivo.2009

    • Author(s)
      Ito A, Ishida T, Utsunomiya A, Sato F, Mori F, Yano H, Inagaki A, Suzuki S, Takino H, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R.
    • Journal Title

      J Immunol. 183

      Pages: 4782-91

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Asn505 mutation of c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity.2009

    • Author(s)
      Ding J, Komatsu H, Iida S, Yano H, Kusumoto S, Inagaki A, Mori F, Ri M, Ito A, Wakita A, Ishida T, Nitta M, Ueda R.
    • Journal Title

      Blood. 114

      Pages: 3325-8

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of the ULBP ligands for NKG2D by B-NHL cells plays an important role in determining their susceptibility to rituximab-induced ADCC.2009

    • Author(s)
      Inagaki A, Ishida T, Yano H, Ishii T, Kusumoto S, Ito A, Ri M, Mori F, Ding J, Komatsu H, Iida S, Ueda R.
    • Journal Title

      Int J Cancer. 125

      Pages: 212-21

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bortezomib-induced apoptosis in mature T-cell lymphoma cells partially depends on upregulation of Noxa and functional repression of Mcl-1.2009

    • Author(s)
      Ri M, Iida S, Ishida T, Ito A, Yano H, Inagaki A, Ding J, Kusumoto S, Komatsu H, Utsunomiya A, Ueda R.
    • Journal Title

      Cancer Sci. 100

      Pages: 341-8

    • NAID

      10025142727

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in the novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model.2009

    • Author(s)
      7. Ito A, Ishida T, Yano H, Inagaki A, Suzuki S, Sato F, Takino H, Mori F, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R.
    • Journal Title

      Cancer Immunol Immunother. 58

      Pages: 1195-206

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary ATLL cells mediated by autologous human immune cells inNOD/Shi-scid,, IL-2R gamma(null)mice in vivo2009

    • Author(s)
      Ito A
    • Journal Title

      J Immunol 183(7)

      Pages: 4782-91

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-CCR4 monoclonal antibody as a novel therapy for advanced mycosis fungoides and Sezary syndrome2009

    • Author(s)
      Yano H
    • Journal Title

      Rinsho Ketsueki 50(12)

      Pages: 1671-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of physicians in charge of cancer chemotherapy in oncological management2009

    • Author(s)
      Kusumoto S
    • Journal Title

      Nippon Naika Gakkai Zasshi 98(8)

      Pages: 1947-51

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small-cell lung cancer arising after chemotherapy for a patient with lymphoma of pulmonary mucosa-associated lymphoid tissue-a case report2009

    • Author(s)
      NaKao M
    • Journal Title

      Gan To Kagaku Ryoho 36(10)

      Pages: 1711-4

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of thymidylate synthase for resistance to pemetrexed in lung cancer2009

    • Author(s)
      Ozasa H
    • Journal Title

      Cacner Sci 101(1)

      Pages: 161-6

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis, enzyme inhibition and tumor cell growth inhibition of 2-anilinobenzamide derivatives as SIRT1 inhibitors2009

    • Author(s)
      Suzuki T
    • Journal Title

      Bloorg Med Chem 17(16)

      Pages: 5900-5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of the ULBP ligands for NKG2D by B-NHL cellsplays an important role in determining their susceptibility to rituximab-induced ADCC2009

    • Author(s)
      Inagaki A
    • Journal Title

      Int J Cancer 125(1)

      Pages: 212-21

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Asn505 mutation of c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mplprotein due to strong amino acid polarity2009

    • Author(s)
      Ding J
    • Journal Title

      Blood 114(15)

      Pages: 3325-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Busulfex(i.v.BU)and CY regimen before SCT : Japanese-targeted phase II pharmacokinetics combined study2009

    • Author(s)
      Kim SW
    • Journal Title

      Bone Marrow Transplant 43(8)

      Pages: 611-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ABCC10/MRP7 is associated with vinorelbine resistance in no n-small cell lung cancer2009

    • Author(s)
      Bessho Y
    • Journal Title

      Oncol Rep 21(1)

      Pages: 263-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of carboxylesterase-2 results in enhanced efficacy of topoisomerase I inhibitor, irinotecan (CPT-11), for multiple myeloma.2008

    • Author(s)
      Yano H, Kayukawa S, Iida S, Nakagawa C, Oguri T, Sanda T, Ding J, Mori F, Ito A, Ri M, Inagaki A, Kusumoto S, Ishida T, Komatsu H, Inagaki H, Suzuki A, Ueda R.
    • Journal Title

      Cancer Sci. 99

      Pages: 2309-14

    • NAID

      10024013572

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Augmentation of antitumour activity of defucosylated chimeric anti-CCR4 monoclonal antibody in SCID mouse model of adult T-cell leukaemia/lymphoma using G-CSF.2008

    • Author(s)
      Yano H, Ishida T, Imada K, Sakai T, Ishii T, Inagaki A, Iida S, Uchiyama T, Ueda R.
    • Journal Title

      Br J Haematol. 140

      Pages: 586-9

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines.2008

    • Author(s)
      Kondo E, Tanaka T, Miyake T, Ichikawa T, Hirai M, Adachi M, Yoshikawa K, Ichimura K, Ohara N, Moriwaki A, Date I, Ueda R, Yoshino T.
    • Journal Title

      Mol Cancer Ther. 7

      Pages: 1461-71

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Combinations of tumor-specific CD8+ CTLs and anti-CD25 mAb provide improved immunotherapy.2008

    • Author(s)
      Ohmura Y, Yoshikawa K, Saga S, Ueda R, Kazaoka Y, Yamada S.
    • Journal Title

      Oncol Rep. 19

      Pages: 1265-70

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of carboxylesterase-2 results in enhanced efficacy of topoisomerse I inhibitor, irinotecan (CPT- 11), for multiple myeloma2008

    • Author(s)
      Yano H
    • Journal Title

      Cancer Sci. 99(11)

      Pages: 2309-14

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model2008

    • Author(s)
      Ito A
    • Journal Title

      Cancer Immunol Immunother (印刷中in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bortwzomib-induced apoptosis in mature T-cell lymphoma cells partially depends on upregulation of Noxa and functional repression of Mcl-1.2008

    • Author(s)
      Ri M
    • Journal Title

      Cancer Sci. (印刷中in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated anti-CCR4 monoclonal antibody combined with immunomodulatory cytokines: a novel immunotherapy for aggressive/ refractory mycosis fungoides and sezary syndrome.2007

    • Author(s)
      Yano H, Ishida T, Inagaki A, Ishii T, Ding J, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R.
    • Journal Title

      Clin Cancer Res. 13

      Pages: 6494-500

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory T-cell Function of adult T-cell leukemia/lymphoma cells.2007

    • Author(s)
      Yano H, Ishida T, Inagaki A, Ishii T, Kusumoto S, Komatsu H, Iida S, Utsunomiya A, Ueda R.
    • Journal Title

      Int J Cancer. 120

      Pages: 2052-7

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Japan Clinical Oncology Group Study JCOG9801. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801.2007

    • Author(s)
      Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M.
    • Journal Title

      J Clin Oncol. 25

      Pages: 5458-64

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic Significance of NPM-ALK Fusion Transcript Overexpression in ALK-positive Anaplastic Large Cell Lymphoma.2007

    • Author(s)
      Li C, Takino H, Eimoto T, Ishida T, Inagaki A, Ueda R, Suzuki R, Yoshino T, Nakagawa A, Nakamura S, Inagaki H.
    • Journal Title

      Mod Pathol. 20

      Pages: 648-55

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Significance of a blood eosinophilia in adult T-cell leukemia/lymphoma: a blood eosinophilia is a significant unfavorable prognostic factor.2007

    • Author(s)
      Utsunomiya A, Ishida T, Inagaki A, Ishii T, Yano H, Komatsu H, Iida S, Yonekura K, Takeuchi S, Takatsuka Y, Ueda R.
    • Journal Title

      Leuk Res. 31

      Pages: 915-20

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differing distributions of CXCR3-andCCR4-positive cells among types of interstit l pneumonia associated with collagen vascular diseases.2007

    • Author(s)
      Shimizu S, Yoshinouchi T, Niimi T, Ohtsuki Y, Fuzita J, Maeda H, Sato S, Yamadori I, Eimoto T, Ueda R.
    • Journal Title

      Virchows Arch. 450

      Pages: 51-8

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of chemokine receptors CXCR3 and CCR4 in lymphocytes of idiopathic nonspecific interstitial pneumonia.2007

    • Author(s)
      Yoshinouchi T, Naniwa T, Shimizu S, Ohtsuki Y, Fujita J, Sato S, Eimoto T, Ueda R.
    • Journal Title

      Respir Med. 101

      Pages: 1258-64

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid.2007

    • Author(s)
      Sanda, T.
    • Journal Title

      Haematologica 92(1)

      Pages: 115-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory T-cell function of adult T-cell leukemia/lymphoma cells.2007

    • Author(s)
      Yano, H.
    • Journal Title

      Int J Cancer 120(9)

      Pages: 2052-2057

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term Follow-up of 14 Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia following Autologous Bone Marrow Transplantation in First Complete Remission2007

    • Author(s)
      Mizuta, S.
    • Journal Title

      Int J Hematol. 85(2)

      Pages: 140-5

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunoglobuiln VH gene analysis in gastric MALT lymphomas.2007

    • Author(s)
      Sakuma, H.
    • Journal Title

      Mod Pathol. 20(4)

      Pages: 460-466

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of NPM-ALKfusion transcript overexpression in ALK-positive anaplastic large-cell Iymphoma2007

    • Author(s)
      Li, C.
    • Journal Title

      Modern Pathology 20

      Pages: 648-655

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of a blood eosinophilia in adult T-cell leuzkemia /lymphoma: a blood eosinophilia is a significant unfavorable prognostic factor.2007

    • Author(s)
      Utsunomiya, A.
    • Journal Title

      Leuk Res. 31(7)

      Pages: 915-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differing distributions of CXCR3-and CCR4 -positive cells among types of interstitial pneumonia associated with collagen vascular diseases.2007

    • Author(s)
      Shimizu, S.
    • Journal Title

      Virchows Arch. 450(1)

      Pages: 51-58

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] VCAP-AMP-VECP Compared With Biweekly CHOP for Adult T-Cell Leukemia-Lymphoma: Japan Clinical Oncology Group Study JCOG9801.2007

    • Author(s)
      Tsukasaki, K.
    • Journal Title

      J Clin Oncol. 25(34)

      Pages: 5458-64

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defucosylated Anti CC Chemokine Receptor 4 Monoclonal Antibody Combined with Immunomodulatory Cytokines: A Novel Immunotherapy for Aggressive/Refractory Mycosis Fungoides and Sezary Syndrome.2007

    • Author(s)
      Yano, H.
    • Journal Title

      Clin Cancer Res. 13(21)

      Pages: 6494-6500

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] POU2AF1, an amplification target at 11q23, priomotes growth of multiple myeloma cells by directly regulating expression of a B-cell maturation factor, TNFRSF17.2007

    • Author(s)
      Zhao, C.
    • Journal Title

      Oncogene 27(1)

      Pages: 63-75

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] CCR4 as a novel specific molecular target for immunotherapy in ATLL.2010

    • Author(s)
      Ueda R.
    • Organizer
      8th AACR/JCB Conference. 5-9 February
    • Place of Presentation
      Waikoloa, Hawaii
    • Related Report
      2009 Final Research Report
  • [Presentation] The CCR4 as a novel specific molecular target for immunotherapy in ATL2008

    • Author(s)
      Ishida, T.
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] Phase I study of KW-0761, a Defucosylated Patients(Pts) with Adult T-Cell Leukemia-Lymphoma(ATLL) or Peripheral T-Cell Lymphoma(PTCL): Updated Results.2008

    • Author(s)
      Yamamoto K, Tobinai K, Utsunomiya A, Tsukasaki K, Uike N, Uozumi K, Tomonaga M, Matsushima K, Shitara K, Akinaga S, Ueda R.
    • Organizer
      The 50th Annual Meeting of American Society of Hematology
    • Place of Presentation
      San Francisco, CA, USA
    • Related Report
      2009 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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