1987 Fiscal Year Final Research Report Summary
T cell and tumor cell purging of marrow cell suspension using monoclonal antibodies - Effect of technique
| Project/Area Number |
60570565
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
AMEMIYA Youichi Jichi Medical School, 医学部, 助教授 (10101338)
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| Co-Investigator(Kenkyū-buntansha) |
KOMATSU Norio Jichi Medical School, 医学部, 助手 (50186798)
TAKAGI Shojiro Jichi Medical School, 医学部, 講師 (20158992)
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| Project Period (FY) |
1985 – 1987
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| Keywords | T cell depletion / Tumor cell purging / Tumor spesific monoclonal antibodies / Bone marrow transplantation / AAABC therapy / FCMによる赤血球抗原の解析 |
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| Research Abstract |
GVHD(grft vs host disease) is a major compication of allogeneic BMT(bone marrow transplantation). It is now well established in animal models that GVHD is mediated by mature T lymphocyte that contaminated the donor marrow cells. Based on this concept, depletion of mature T lymphocyte from the donor hematopoietic cells would effectively reduce the incidence and severity of acute GVHD as well as in humans.
It is to be expected that the relapse rate after high-dose cytoreduction and autologous BMT will be higher than after allogeneic BMT because of contaminated tumor cell in inoculation marrow.
Although various methods are used for elimanating tumor cells or T cells from bone marrow cell suspensions,immunological technigues based on MCA(monoclonal antibodies)has been chosen in this study,and the present study was desiged to complete basic conditions on this procceding.
Complement-dependent microcytotoxicity test was available for evaluation of MCA spesificity against target cells and human c
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omplement activity. And also indirect immunofluorescence assay with flowcytometry was performed. The low recovery of hematopoietic stem cells resulting from depleting target cells and cryopreserve-thawing marrow cells is one of the most important prpblems. With a view to improving this recovery rate, we examined whether isoproterenol drug could act on mouse and human bone narrow cells. From the present findings that isoproterenol acted on bone marrow cells in such a way as to increase the number of colonies in hematopoietic stem cell, we conclude that isoproterenol may stimulate DNA synthesis and enhance the proliferation of hematopoietic stem cells.
A AAABC preconditioning regimen which is consisted of ADR,ACNU,Ara-C,BLM,cyclophosphamide drugs was deviced for autologous BMT, showing that a prolonged remission in patients with malignant lymphoma in whom conventional chemotherapy has failed has been experienced.
Immunological reconstitution was studied with regard to T cell subsets in patients who received BMT. One of the distinct features was the imbalance of T cell subsets. Long standing inversion of CD4/CD8 ratio was characteristic in both autologous and allogeneic BMT patients.
This protocol is still under investigation,then further clinical studies are required. Less
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