| Project/Area Number |
14370520
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
TACHIBANA Masaaki Medical University, Medicine, Professor, 医学部, 教授 (70129526)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Kunihiko Medical University, Medicine, Assistant Professor, 医学部, 講師 (60220589)
NAMIKI Kazunori Medical University, Medicine, Assistant Professor, 医学部, 講師 (40256243)
OHNO Yoshio Medical University, Medicine, Professor, 医学部, 講師 (40266482)
MUKAI Kiyoshi Medical University, Medicine, Professor, 医学部, 教授 (20190837)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Immunocyto therapy / Dendritic cells / CD34+progenitor cells / Prostate cancer / Bladder cancer / Renal cell carcinoma / 腎細胞癌 / 同種抹消血幹細胞 / 癌特異抗原 / エピトープペプチド / 同種末梢幹細胞 / 進行癌 / 抗原決定基蛋白 / 前立腺膜特異抗原 |
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| Research Abstract |
In order to develop a less invasive treatment strategy for advanced urological cancer, we. examined the potential of cell-immunotherapy using dendritic cells (DCs) generated from peripheral blood mono nuclear cells of kinsman. 2002 as a, we synthesized HLA-A2 and -A24 restricted epitope peptides prostate specific membrane antigen epitope peptide for prostate cancer and melanoma antigen-3 epitope peptide for bladder cancer. DCs loaded with each major histocompatibility antigen class 1 restricted epitope peptide were able to induce corresponding antigen- specific cytotoxic T-lymphocytes capable to lyse the target cancer cells in vitro. The immunotherapy using autologous monocyte-derived DCs loaded with these epitope peptides, which was introduced to at least either HLA-A2 or -A24 positive patients with bladder cancer and prostate cancer in preceding year, was carried out through second fiscal year 2003. There were patients showed a >50% reduction in the size of metastatic tumor or in ser
… More
ological tumor marker. No severe adverse effect was observed in all patients treated with this therapy. These results suggested that the DC based immunotherapy was safe and, effective for patients with cancer resistant to conventional treatment. We also identified novel cancer specific antigens of bladder cancer by using serologic identification of recombinant cDNA expression cloning method, and synthesized the HLA -A24 restricted epitope peptides of these antigens. It was possible to elicit HLA-A24 positive bladder cancer cell lysis by DCs loaded with these epitope peptides in vitro. As for the main purpose of this study, the induction of DCs from allogeneic peripheral stem cells, we demonstrated that CD34 positive progenitor cells were separated from peripheral blood with the purity of 85.3% by using magnetic cell selection system. This made it appear that the application of this system enables to make cell conditioning more efficient. Furthermore, to examine the effect of DCs generated from allogeneic CD34 progenitor cells to the donor lymphocytes, we carried out mixed culture experiment using DCs from one of twin, lymphocytes from the other of twin, parents and non-kinsman in the same way of mixed lymphocyte culture. The rejection test of DCs by the lymphocytes of non-kinsman showed that the stimulation index was 3.6 comparable to the results in kin group. This result suggested that it might not be necessary to limit the source of DCs to CD34 progenitor cells from kinsman. Less
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