| Project/Area Number |
07671587
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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 |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
ARAKI Nobuhito Osaka University Medical School, Assistant Professor, 医学部, 助手 (10252678)
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| Co-Investigator(Kenkyū-buntansha) |
KURATSU Shigeyuki Osaka University Medical School, Assistant Professor, 医学部, 助手 (20273683)
内田 淳正 大阪大学, 医学部, 助教授 (40176681)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | malignant bone and soft tissue tumor / immunotherapy / chemotherapy / tumor infiltrating lymphocyte / T cell receptor / synovial sarcoma / SYT-SSX / fugion gene / 腫瘍内浸潤リンパ球 / fusion gene / fusion gen |
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| Research Abstract |
The purpose of this study is to establish a new therapy using the tumor specific antigens. First, we planed to establish a monoclonal T cell clone that recognize the tumor specific antigen. We could expand TIL (tumor infiltrating lymphocyte) effectively from operatively resected tumor tissue that locally immunized with OK432 preoperatively. However, the expansion could be successfully continued only in 30%. Also, the TIL clonality was not high enough to analyze the T cell repator that recognize the tumor specific antigen. Therefore, next, we started to isolate the tumor specific antigen from the view point of the tumor specific gene rearrangement such as the fusion genes in soft tissue sarcomas. We examined the SYT-SSX fusion gene in synovial sarcoma and clarified that this fusion gene expression is quite specific in synovial sarcoma and that the expression could not seen in any other sarcomas. So, this gene product can be considered as a tumor specific antigen in our immuno-gene therapy. Then, we made the polyclonal antibody to the SYT-SSX fusion gene product using the C terminal of the amino acids sequence. The antibody obtained clearly showed a 60kDa band on the immuno-precipitation assay. Also, we confirmed the tumorigenesity of this fusion gene with the transection of the gene to NIH3T3 cells in vitro and in vivo. These data suggested that the SYT-SSX fusion gene is the specific key gene of synovial sarcoma and might be used as the tumor specific therapy. As the first step of the essential therapy to synovial sarcoma, we used antisense oligonucleotide of this fusion gene in vitro. There was a significant suppression of tumor growth compared to the control cells and to the control oligonucleotide. However, the efficacy was not high enough to utilize this method to human synovial sarcoma, it is necessary to establish more effective method to utilize this tumor specific gene rearrangement and the product.
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