1999 Fiscal Year Final Research Report Summary
Differentiation of dendritic cells and their use for tumor immunology
| Project/Area Number |
09671119
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
OTSUKA Teruhisa Kyushu University, Medicine, Assistant Professor, 医学部, 講師 (20185317)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Yoshikiyo Kyushu University, Medicine, Medical Stuff, 医学部, 医員
SUGIO Yasuhiro Kyushu University, Medicine, Medical Stuff, 医学部, 医員
MAEDA Motoi Kyushu University, Medicine, Medical Stuff, 医学部, 医員
IINO Tadafumi Kyushu University, Medicine, Medical Stuff, 医学部, 医員
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| Project Period (FY) |
1997 – 1999
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| Keywords | dendritic cell / tumor immunology / AML1 / MTG8 / cytotoxic T-cell / クリオグロブリン血症 |
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| Research Abstract |
We succeeded to generate dendritic cells from adherent peripheral blood mononuclear cells cultured with rhGM-CSF, rhIL-4 and rhTNF-alfa. After 10days, the cultured cells, which display the typical cell surface markers of mature monocyto-derived dendritic cells (Mp-DCs) and induce T cells to make primary and secondary immune response are harvested. Then, we tried to identify the tumor antigen of acute leukemia using Mo-DCs. We made the hypothesis that the overexpression of the MTG8 gene in t (8 ; 21) AML cells could act as a possible tumor antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b aa182-191) using Mo-DCs from a healthy donor. T cell receptor (TCR) Vα17, TCRVβ14 and 15, and TCRJβ2.1 and 2.3 are predominantly used in these CTL lines. Our data which suggest that the MTG8 protein could be one of the tumor antigens recognized by CTLs may be helpful in further investigations of TCR analysis in t (8 ; 21) AML patients with HLA-A0201 who are in long-term remission. Finally, we vaccinated a refractory essential monoclonal cryoglobulinemia patient with Mo-DCs pulsed with purified cryoglobulin as a tumor antigen. During the vaccinations, his acrocyanosis improved and we were able to reduce the number of hot baths used to treat his symptoms, with no side effect. Furthermore, cryoglobulin-specific proliferative responses were observed after the vaccination. As there was a recurrence of acrocyanosis after the final vaccination, vaccination with Mo-DCs pulsed with purified cryoglobulin would seem to be a useful treatment for refractory essential monoclonal cryoglobulinemia.
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