2010 Fiscal Year Final Research Report
Overcome to avoidance from the anti-leukemia immunity by using combination therapy with HSP and dendritic cells targeted to both tumor and tumor angiogenesis
| Project/Area Number |
20591143
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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 | Asahikawa Medical College |
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Principal Investigator |
SATO Kazuya Asahikawa Medical College, 医学部, 講師 (50360988)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUKAMI Yuusuke 旭川医科大学, 医学部, 講師 (30400089)
OHTAKE Takaaki 旭川医科大学, 医学部, 講師 (10359490)
IKUTA Katsuya 旭川医科大学, 医学部, 講師 (00396376)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 腫瘍血管内皮 / 熱ショック蛋白(HSP) / VEGF / 白血病特異免疫 / 腫瘍血管新生 / 細胞不死化 / IGF |
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| Research Abstract |
In this study, we tried induction of the anti-leukemia immunity by using heat shock protein (HSP) targeted to both tumor and tumor angiogenesis. We demonstrated the presence of tumor angiogenesis in the A20-bearing mouse by endothelium cell (EC)-marker CD31 immunostaining. It was difficult to obtain the enough amount of EC by MACS with anti-CD31 antibody (Ab). We therefore originated GFP transduced A20-cells, and then GFP-negative fraction was sorted from A20-tumor tissue. Now we tried to separate the A20-tumor-associated EC (A20-EC) by using sorted GFP-negative fraction. To increase the number of EC, a vector containing immortalizing gene teromerase reverse transcriptase (TERT) was constructed. After successful A20-EC separation, transduction of TERT gene to A20-ESs and expansion of them will be performed, and then purification of A20-EC-derived HSP will be planed. To obtain the useful information of tumor endotherial antigen in the B-cell neoplasms, the specimen of solitary plasmacytoma in POEMS syndrome, which is known as one of the angiogenic B-cell neoplasms, was immunostained with angiogenic factors, and we demonstrated that the expression levels of VEGF and IGF were very high in the tumor. In addition, we showed the possibility that anti-idiotype Ab of mouse B-cell neoplasm may inhibit the angiogenesis in the microenvironment of the B-cell tumor through humoral immunity by the CDC. These findings enable the approach by novel immunotherapy against tumor ECs with unique motifs, such as HSPs derived from B-cell neoplasm associated ECs or anti-idiotype Ab.
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Research Products
(4 results)
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[Journal Article] Development of POEMS syndrome after an initial manifestation of solitary plasmacytoma2011
Author(s)
Shindo M, Sato K, Yamamoto M, Toki Y, Hatayama M, Ito S, Ichiki K, Okamura N, Hosoki T, Ikuta K.Inamura J, Watanabe S, Torimoto Y, Kohgo Y
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Journal Title
Int J Hematol. (Epub ahead of print)
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