Investigation of acquired resistance of PD-1 inhibitor with recycle of CART system
| Project/Area Number |
17K19591
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安彦 郁 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (20508246)
村上 隆介 京都大学, 医学研究科, 特定病院助教 (40782363)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 卵巣癌 / がん性腹水 / CART / 腫瘍免疫 / CARTシステム / 癌性腹水 / 腹水濾過濃縮再静注療法（CART） / 免疫逃避 / 癌 / 免疫学 |
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| Outline of Final Research Achievements |
A large amount of cancer ascitic fluid could be filtrated and be concentrated by CART system in the patients with recurrent ovarian cancer. The optimal extraction of cancer cells and immune cells from the cancer ascites and next, we identified the several genes associated with chemotherapy-resistance. Mouse ovarian cancer cell lines whose expression was suppressed in syngeneic mouse ovarian cancer cell lines for these genes. Cancer ascites model and combined treatment with an inhibitor of these genes significantly reduced cancer ascites and prolonged survival. Similar results were obtained in an immunodeficient PDX model administered with cancer ascites cells collected by CART. The results show the usefulness of monitoring and reuse of the CART method for immune analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では卵巣癌だけでなく、がん性腹水を生じる他臓器がんにも応用可能であると考えられるため、CART法による、腫瘍局所の多角的な免疫状態のモニタリングや、新たな免疫抑制因子の発現メカニズムの解明、さらには同因子を標的とした新たな治療選択のシーズ開発の基盤として、様々な再利用（リサイクル）が複数のがん種に対して期待でき、限られた医療材料や資源を有効に活用することが示され、今後の腫瘍免疫研究の新たなツールとして期待できる。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.2020
Author(s)
Horikawa N, Abiko K, Matsumura N, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Ukita M, Hosoe Y, Koshiyama M, Konishi I, Mandai M.
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Journal Title
Br J Cancer.
Volume: 122(1)
Issue: 6
Pages: 778-788
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.2019
Author(s)
Yamanoi K, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Hosoe Y, Murphy SK, Konishi I, Mandai M, Matsumura N.
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Journal Title
Sci Rep.
Volume: 9(1)
Issue: 1
Pages: 14215-14215
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma.2019
Author(s)
Goto M, Chamoto K, Higuchi K, Yamashita S, Noda K, Iino T, Miura M, Yamasaki T, Ogawa O, Sonobe M, Date H, Hamanishi J, Mandai M, Tanaka Y, Chikuma S, Hatae R, Muto M, Minamiguchi S, Minato N, Honjo T
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 10144-10144
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Phosphorylation of STAT1 Serine 727 Enhances Platinum Resistance in Uterine Serous Carcinoma.2019
Author(s)
Zeng X, Baba T, Hamanishi J, Matsumura N, Budiman K, Mise Y, Abiko K, Yamaguchi K, Horikawa N, Huntsman DG, Mulati K, Kitamura S, Taki M, Murakami R, Hosoe Y, Mandai M.
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Journal Title
Int J Cancer.
Volume: 145(6)
Issue: 6
Pages: 1635-1647
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] VISTA expressed in tumour cells regulates T cell function2018
Author(s)
Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
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Journal Title
British Journal of Cancer
Volume: 120
Issue: 1
Pages: 115-127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.2018
Author(s)
Taki M, Abiko K, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Yamanoi K, Horikawa N, Hosoe Y, Nakamura E, Sugiyama A, Mandai M, Konishi I, Matsumura N.
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Journal Title
Nature communications
Volume: Apr 27;9(1)
Issue: 1
Pages: 1685-1685
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression.2018
Author(s)
Lin H, Wei S, Hurt EM, Green MD, Zhao L, Vatan L, Szeliga W, Herbst R, Harms PW, Fecher LA, Vats P, Chinnaiyan AM, Lao CD, Lawrence TS, Wicha M, Hamanishi J, Mandai M, Kryczek I, Zou W.
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Journal Title
J Clin Invest
Volume: Apr 2;128(4)
Issue: 4
Pages: 1708-1708
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks.2017
Author(s)
Murakami R, Matsumura N, Brown JB, Higasa K, Tsutsumi T, Kamada M, Abou-Taleb H, Hosoe Y, Kitamura S, Yamaguchi K, Abiko K, Hamanishi J, Baba T, Koshiyama M, Okuno Y, Yamada R, Matsuda F, Konishi I, Mandai M.
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Journal Title
The American Journal of Pathology
Volume: 187
Issue: 10
Pages: 2246-2258
DOI
Related Report
Peer Reviewed / Open Access
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