Analysis of tumor-infiltrating lymphocytes in malignant gynecologic tumors for development of personalized tumor immunotherapy
Project/Area Number |
16H05472
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Nagoya University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
梶山 広明 名古屋大学, 医学系研究科, 准教授 (00345886)
鈴木 史朗 名古屋大学, 医学部附属病院, 講師 (20612758)
中面 哲也 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (30343354)
柴田 清住 名古屋大学, 医学系研究科, 准教授 (90335026)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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Keywords | 婦人科がん / 腫瘍免疫 / 腫瘍浸潤リンパ球 / 卵巣癌 / 免疫療法 / PDXモデル / TIL |
Outline of Final Research Achievements |
In order to develop personalized immunotherapy for malignant gynecologic tumors, we aimed to characterize tumor infiltrating lymphocytes (TIL) and to clarify the mutated neoantigens of individual patients with malignant gynecologic tumors. Although TIL yield varied between patient samples, we could expanded the TILs from the small fragments of tumor in most cases (97.6%). A total of 14 patient derived xenografts (PDX) models were established. It could be confirmed that the reactive cells to autologous tumor cells were present in the expanded TILs. In two cases with ovarian cancer, we identified candidates of mutated neoantigens by the next generation sequencing combined with bioinformatics prediction and evaluated TILs from the same patients.
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Academic Significance and Societal Importance of the Research Achievements |
TILに由来する個別化療法は症例によっては根治につながる可能性がある。同治療法の出発点は臨床検体採取にあり、婦人科がん手術の適応判断を含めて実行するのは婦人科医であることから、今後も婦人科がんの特徴に合わせた複合的治療戦略やTIL選別・培養方法改良等の基礎的検討が重要であると考えられる。 また、本研究の副産物として構築されるPDX細胞株ライブラリーは、患者の細分化を行うと前向き臨床試験が計画しづらい症例数となってしまう婦人科領域においては、免疫療法開発に限定せずにPrecision Medicineの実践という局面での前臨床試験モデルとしての活用が期待される。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] PAI-1 secreted from metastatic ovarian cancer cells triggers the tumor-promoting role of the mesothelium in a feedback loop to accelerate peritoneal dissemination.2019
Author(s)
Peng Y, Kajiyama H, Yuan H, Nakamura K, Yoshihara M, Yokoi A, Fujikake K, Yasui H, Yoshikawa N, Suzuki S, Senga T, Shibata K, Kikkawa F.
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Journal Title
Cancer Lett
Volume: 442
Pages: 181-192
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Establishment of an antibody specific for cancer-associated haptoglobin: A possible implication of clinical investigation.2018
Author(s)
Nishino K, Koda S, Kataoka N, Takamatsu S, Nakano M, Ikeda S, Kamamatsu Y, Morishita K, Moriwaki K, Eguchi H, Yamamoto E, Kikkawa F, Tomita Y, Kamada Y, Miyoshi E.
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Journal Title
Oncotarget
Volume: 9
Issue: 16
Pages: 12732-12744
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer.2017
Author(s)
Yokoi A, Yoshioka Y, Yamamoto Y, Ishikawa M, Ikeda SI, Kato T, Kiyono T, Takeshita F, Kajiyama H, Kikkawa F,
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Journal Title
Nat Commun.
Volume: 6
Issue: 1
Pages: 14470-14470
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] A recurrence-predicting prognostic factor for patients with early-stage epithelial ovarian cancer undergoing fertility-sparing surgery2016
Author(s)
梶山 広明,柴田 清住, 坂田 純, 内海 史, 新美 薫, 関谷 龍一郎, 鈴木 史朗, 藤掛 佳代, 吉原 雅人, 関谷 敦史, 玉内 学志, 吉川 史隆
Organizer
日本癌治療学会学術集会
Place of Presentation
パシフィコ横浜(神奈川県横浜市)
Year and Date
2016-10-21
Related Report
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