2005 Fiscal Year Final Research Report Summary
Anti-tumor immunity after non-myeloablative cord blood cell transplantation for Adult T cell leukemia/lymphoma
| Project/Area Number |
16590926
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
UCHIMARU Kaoru The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (60251203)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Satoshi The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (60226834)
OYAIZU Naoki The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (00282773)
WATANABE Toshiki The University of Tokyo, Dept of Medical Genome Science, Professor, 医科学研究所, 教授 (30182934)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Adult T cell leukemia / lymphoma / Cord Blood Cell Transplantation / Non-myeloablative Stem Cell Transplantation / Proviral load |
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| Research Abstract |
In this study, we performed allogeneic stem cell transplantation for 2 lymphoma type ATL patients (one CBT by conventional conditioning and one related. PBSCT by non-myeloablative conditioning). Residual disease was evaluated by HTLV-1 proviral load in PB. In case 1 who received CBT, proviral load reached to the undetectable level at day 60 after CBT. Provirus could be detected after day 100 but its load remained at low level below 3 copies/ 1000 MNCs. In the second case of RIC-PBSCT, provirus in PB couldn't be detected after 130 days from SCT. Peripheral blood of these patients before and after SCT was collected to evaluate immune response to HTLV-1 after SCT. Although we tried to establish HTLV-1 infected cell lines from their PBMNCs, cell lines have not been established. Activation of T cells with CD3/CD28 may facilitate infection and now we are trying to culture MT-2 with activated T cells with/without various cytokines such as IL-2, IL-10, TGF-b.
Distribution of tumor cells in patients with lymphoma type ATL was largely unknown. Using tumor cell specific PCR, we tried to detect major clone of lymphoma in their PB. In brief, genomic DNA was extracted from their tumor specimen and we expand DNA flanking to HTLV-1 integration site by Inverse-Long PCR method. After determining the sequence and production of specific primer set, we tried to detect tumor cell in the PB by PCR. We could detect tumor cells in their PB and these cells disappeared after SCT. We further examined PB samples of 20 ATL patients. In 2 patients, we detected different clones from the previous ones detected before chemotherapies, which suggested polyclonal tumorigenesis of ATL. Now we are planning to examine clonal change after SCT.
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