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Development of virus-specific immunocellular therapy after cord blood transplantation

Research Project

Project/Area Number 17590981
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHASHI Satoshi  The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (60226834)

Co-Investigator(Kenkyū-buntansha) KATO Kazunori  Sapporo Medical University, Associate Professor, 医学部, 助教授 (60233780)
WATANABE Nobukazu  The University of Tokyo, Institute of Medical Science, COE Clinical Associate, 医科学研究所, 特任助手 (10334278)
TOJO Arinobu  The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (00211681)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsCord blood transplantation / Cytomegalovirus / Immune reconstitution / Effector cell / Memory cell / Tetramer / Cell therapy / Targeting / メモリー / ナイーブ / アデノウイルスベクター
Research Abstract

The one of crucial questions in cord blood transplantation (CBT) is whether naivity of cord blood lymphocytes could gain antigen-specific cellular immunity during early phase of transplant. Cytomegalovirus (CMV) infection is serious clinical problem in allogeneic transplant recipients and T cell immunity has known to have an important. role in control of virus replication and prevention.
During 1998 and 2006, 111 adults has received myeloablative regimens including 12 Gy of total body irradiation followed by CBT and a standard cyclosporine and methotrexate combination as GVHD prophylaxis in our institute. Patients also received intravenous immunoglobulin from day -3 to day 120 if the immunoglobulin level in the serum was less than 500 mg/dl. CMV antigenemia assay was performed twice a week after neutrophil recovery until day 120. Once CMV antigenemia is positive, patients received 5 mg/kg ganciclovir (GCV) once daily for at least 2 weeks as preemptive therapy. Ninety-two patients achiev … More ed engraftment with full donor chimerism and survived without disease relapse at the time of 120 days after CBT (82.8%). None of these 92 recipients had CMV disease during first 4 months after CBT.
We have investigated the association of CMV reactivation status and their immune reconstitution process for 4 months after CBT in 39 patients who received CBT from 2002 to 2006 in our institute. CMV-specific CD4^+ and CD8^+ T cell recoveries were assessed by detection of interferon-g (IFN-g) producing cells with CMV antigen stimulation using intracellular cytokine staining. The positive was defined as more than 0.1% IFN-g positive cells among CD4^+ or CD8^+ T population.
Six of 39 patients were CMV sero-negative and 33 patients were sero-positive. None of 6 CMV sero-negative recipients and 31 of 33 CMV sero-positive recipients observed CMV reactivation and received GCV therapy within the first 4 months. CMV-specific CD4^+ T cells were detected in 30 of 31 recipients with positive CMV antigenemia (% positive:55% at 1 month and 85% at 2 month), on the other hand, CMV-specific CD8^+ T cells were detected in 14 out of 31 cases (% positive:14% at 1 month and 22% at 2 month), both of which were comparable to post-bone marrow or peripheral blood transplants (CMV-specific CD4^+ T cells were detected 18 of 21 recipients with positive CMV antigenemia and CMV-specific CD8^+ T cells were detected in 12 out of 21).
These data suggest that post-thymic naive T lymphocytes in cord blood might obtain memory and effector function in vivo with antigen-specific manner during early phase of post-transplant. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (32 results)

All 2007 2006 2005

All Journal Article (32 results)

  • [Journal Article] Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem cell transplantation from related donors in adult patients with hematological malignancies after myeloablative conditioning regimen2007

    • Author(s)
      Takahashi S, Tojo A, et al.
    • Journal Title

      Blood 109

      Pages: 1322-1330

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem cell transplantation from unrelated donors in adult patients with hematologicalmalignancies after myeloablative conditioning regimen2007

    • Author(s)
      Takahashi S, Tojo A, et al.
    • Journal Title

      Blood 109

      Pages: 1322-1330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Post-transplant engraftment and safety of cord blood transplantation with grafts containing relatively low cell doses in adults.2006

    • Author(s)
      Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 84

      Pages: 359-362

    • NAID

      10019259789

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pancreatic hyperamylasemia and hyperlipasemia in association with cytomegalovirus infection following unrelated cord blood transplantation for acute myelogenous leukemia.2006

    • Author(s)
      Fukuno K, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 84

      Pages: 438-440

    • NAID

      10018671012

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning in patients with acute leukemia aged between 50 and 55 years.2006

    • Author(s)
      Konuma T, Ooi J, Takahashi S, Tojo A, et al.
    • Journal Title

      Bone Marrow Transplant 37

      Pages: 803-804

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Early-onset thyrotoxicosis after unrelated cord blood transplantation for acute myelogenous leukemia.2006

    • Author(s)
      Konuma T, Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 83

      Pages: 348-350

    • NAID

      10017475721

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Varicella-zoster virus encephalitis in a patient undergoing unrelated cord blood transplantation for myelodysplastic syndrome-overt leukemia.2006

    • Author(s)
      Fukuno K, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 84

      Pages: 79-82

    • NAID

      10020357927

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hemorrhagic cystitis in adults after unrelated cord blood transplantation : a single-institution experience in Japan.2006

    • Author(s)
      Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 84

      Pages: 268-271

    • NAID

      10018304165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cord blood transplantation for acute myelogenous leukemia using a conditionin regimen consisting of granulocyte colony-stimulating factor-combined high-dose cytarabine, fludarabine, and total body irradiation.2006

    • Author(s)
      Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Eur J Haematol 77

      Pages: 46-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Post-transplant engraftment and safety of cord blood transplantation with grafts containing relatively low cell doses in adults.2006

    • Author(s)
      Takahashi s, Tojo A, et al.
    • Journal Title

      Int H Hematol 84

      Pages: 359-362

    • NAID

      10019259789

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pancreatic hyperamylasemia and hyperlipasemia in association with cytomegalovirus infection following unrelated cord blood transplantation for acute myelogenous leukemia.2006

    • Author(s)
      Fukuno K, Tomonar A, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol. 84

      Pages: 438-440

    • NAID

      10018671012

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Varicella-zoster virus encephalitis in a patient undergoing unrelated cord blood transplantation for myelodysplastic syndrome-overt leukemia.2006

    • Author(s)
      Fukuno K, Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol. 84

      Pages: 79-82

    • NAID

      10020357927

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning in patients with acute leukemia aged between 50 and 55 years.2006

    • Author(s)
      Konuma T, Ooio J, Takahashi S, Tojo A, et al.
    • Journal Title

      Bone Marrow Transplant. 37

      Pages: 803-804

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Successful cord blood transplantation for myelodysplastic syndrome resulting in resolution of pulmonary alveolar proteinosis.2006

    • Author(s)
      Fukuno K, Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Bone Marrow Transplant. 38

      Pages: 581-582

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hemorrhagic cystitis in adults after unrelated cord blood transplantation : a single-institution experience in Japan.2006

    • Author(s)
      Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol. 84

      Pages: 268-271

    • NAID

      10018304165

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cord blood transplantation for acute myelogenous leukemia using a conditioning regimen consisting of granulocyte colony-stimulating factor-combined high-dose cytarabine, fludarabine, and total body irradiation.2006

    • Author(s)
      Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Eur J Hematol. 77

      Pages: 46-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Early-onset thyrotoxicosis after unrelated cord blood transplantation for acute myelogenous leukemia.2006

    • Author(s)
      Konuma T, Takahashi S, et al.
    • Journal Title

      Int J Hematol 83

      Pages: 348-50

    • NAID

      10017475721

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hemorrhagic cystitis in adults after unrelated cord blood transplantation : a single-institution experience in Japan.2006

    • Author(s)
      Tomonari A, Takahashi S, et al.
    • Journal Title

      Int J Hematol. 84

      Pages: 268-271

    • NAID

      10018304165

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cord blood transplantation for acute myelogenous leukemia using a conditioning regimen consisting of granulocyte colony-stimulating factor-combined high-dose cytarabine, fludarabine, and total body irradiation.2006

    • Author(s)
      Tomonari A, Takahashi S, et al.
    • Journal Title

      Eur J Haematol. 77

      Pages: 46-50

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning in patients with acute leukemia aged between 50 and 55 years.2006

    • Author(s)
      Konuma T, Takahashi S, et al.
    • Journal Title

      Bone Marrow Transplant. 37

      Pages: 803-804

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Post-transplan engraftment and safety of cord blood transplantation with grafts containing relatively low cell doses in adults.2006

    • Author(s)
      Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 84

      Pages: 359-362

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning for patients with refractory anemia.2005

    • Author(s)
      Ooi J, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol

      Pages: 424-427

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Unrelated cord blood transplantation for a human immunodeficiency virus-1-seropositive patients with acute lymphoblastic leukemia.2005

    • Author(s)
      Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Bone marrow transplant 36

      Pages: 261-262

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cord blood transplants for adults using myeloablative regimens2005

    • Author(s)
      Takahashi S
    • Journal Title

      Biol Blood Marrow Transplant 11

      Pages: 928-929

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human herpesvirus 6 variant B infection in adult patients after unrelated cord blood transplantation.2005

    • Author(s)
      Tomonari A, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 81

      Pages: 352-355

    • NAID

      10015652251

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning for patients with refractory anemia.2005

    • Author(s)
      Ooi J, Takahashi S, Tojo A, et al.
    • Journal Title

      Int J Hematol 81

      Pages: 424-427

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cord blood transplants for adults using myeloablative regimens.2005

    • Author(s)
      Takahashi S
    • Journal Title

      Biol Blood Marrow Transplant 11

      Pages: 928-929

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of Conditioning Regimen on the Outcome of Bone Marrow Transplantation from an Unrelated Donor.2005

    • Author(s)
      Kanda Y, Takahashi S, et al.
    • Journal Title

      Biol Blood Marrow Transplant 11

      Pages: 881-889

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Human herpesvirus 6 variant A infection with fever, skin rash, and liver dysfunction in a patient after unrelated cord blood transplantation.2005

    • Author(s)
      Tomonari A, Takahashi S, et al.
    • Journal Title

      Bone Marrow Transplant 36

      Pages: 1109-1110

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Human herpesvirus 6 variant B infection in adult patients after unrelated cord blood transplantation.2005

    • Author(s)
      Tomonari A, Takahashi S, et al.
    • Journal Title

      Int J Hematol 81

      Pages: 352-355

    • NAID

      10015652251

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Unrelated cord blood transplantation for a human immunodeficiency virus-1-seropositive patients with acute lymphoblastic leukemia.2005

    • Author(s)
      Tomonari A, Takahashi S, et al.
    • Journal Title

      Bone marrow transplant 36

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning for patients with refractory anemia.2005

    • Author(s)
      Ooi J, Takahashi S, et al.
    • Journal Title

      Int J Hematol 81

      Pages: 424-427

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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