Control of pediatric cancer cell proliferation by targetting immune checkpoint proteins
Project/Area Number |
17H04355
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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 |
Pediatric surgery
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Research Institution | Keio University |
Principal Investigator |
KURODA Tatsuo 慶應義塾大学, 医学部(信濃町), 教授 (60170130)
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Co-Investigator(Kenkyū-buntansha) |
田口 智章 福岡医療短期大学, 歯科衛生学科, 学長 (20197247)
渕本 康史 慶應義塾大学, 医学部(信濃町), 特任教授 (40219077)
大喜多 肇 慶應義塾大学, 医学部(信濃町), 准教授 (50317260)
清水 隆弘 慶應義塾大学, 医学部(信濃町), 助教 (80626705)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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Keywords | 小児がん / 免疫チェックポイント蛋白 / 免疫療法 / 腫瘍幹細胞 / PD-1 / PD-L1 / 免疫チェックポイント阻害 / 小児がん腫瘍幹細胞・微小転移細胞の増殖抑制 / 癌 / 外科 / 病理学 |
Outline of Final Research Achievements |
In a pediatric metastatic cancer model using osteosarcoma cell line LM8 cells transplanted to C3H mice, efficacy of the immunotherapy by inhibiting immune check-point protein using anti-PDL1 antibody and Tim-3 antibody with simultaneous immune activation by OX-40 was verified. The mice treated by the present immunotherapy showed significantly longer survival and regression of lung metastases. The mice that received resection of the primary lesion with the additional immunotherapy showed significantly longer survival compared to those treated by surgery alone or immunotherapy alone. The efficacy of the present immune therapy was dependent on residual tumor burden. On the other hand, pathological review of pediatric cancer tissues showed little expression of immune check-point protein and its related molecules at every stage of the treatment. The present study indicated the efficacy of immunotherapy with immune activation in pediatric cancers.
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Academic Significance and Societal Importance of the Research Achievements |
従来、PD1,PDL1の発現や細胞表面抗原の変異が少ないために免疫チェックポイント蛋白阻害療法の効果に疑問がもたれていた小児がんで、免疫賦活を併用することでこの免疫療法が有用であることを示した点で大きな意義があると考える。また従来は原発巣の切除は転移装が制御された場合に適応とされていたが、免疫療法を組み合わせることにより、腫瘍残存量を基盤に小児がん集学的治療の組み立てを根幹から見直させる大きな意義をもつものと考えられた。
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Report
(5 results)
Research Products
(45 results)
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[Journal Article] Fluorescence-Guided Surgery for Hepatoblastoma with Indocyanine Green.2019
Author(s)
Yamada Y, Ohno M, Fujino A, Kanamori Y, Irie R, Yoshioka T, Miyazaki O, Uchida H, Fukuda A, Sakamoto S, Kasahara M, Matsumoto K, Fuchimoto Y, Hoshino K, Kuroda T, Hishiki T.
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Journal Title
Cancers (Basel)
Volume: 11(8)
Pages: E1215
DOI
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Peer Reviewed
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[Journal Article] Rituximab Induction to Prevent the Recurrence of PSC After Liver Transplantation-The Lessons Learned From ABO-Incompatible Living Donor Liver Transplantation.2018
Author(s)
Yamada Y, Hoshino K, Fuchimoto Y, Matsubara K, Hibi T, Yagi H, Abe Y, Shinoda M, Kitago M, Obara H, Yagi T, Okajima H, Kaido T, Uemoto S, Suzuki T, Kubota K, Yoshizumi T, Maehara Y, Inomata Y, Kitagawa Y, Egawa H, Kuroda T.
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Journal Title
Transplant Direct.
Volume: 4(2)
Pages: e342
DOI
Related Report
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[Journal Article] Successful living donor liver retransplantation for graft failure within 7 days due to acute de novo donor-specific anti-human leukocyte antigen antibody-mediated rejection.2018
Author(s)
Yamada Y, Hoshino K, Mori T, Kawaida M, Abe K, Ishihama H, Shimizu T, Takahashi N, Matsubara K, Hibi T, Abe Y, Yagi H, Shimojima N, Shinoda M, Kitago M, Obara H, Fuchimoto Y, Kameyama K, Kitagawa Y, Kuroda T.
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Journal Title
Hepatol Res.
Volume: 48(3)
Pages: E360-E366
DOI
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[Journal Article] Successful management of living donor liver transplantation for biliary atresia with single ventricle physiology-from peri-transplant through total cavopulmonary connection: A case report.2018
Author(s)
Yamada Y, Hoshino K, Oyanagi T, Gatayama R, Maeda J, Katori N, Fuchimoto Y, Hibi T, Shinoda M, Matsubara K, Obara H, Aeba R, Kitagawa Y, Yamagishi H, Kuroda T.
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Journal Title
Pediatr Transplant.
Volume: 22(3)
Pages: e13118
DOI
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[Journal Article] Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes.2017
Author(s)
Yamada Y, Kuda M, Kohashi K, Yamamoto H, Takemoto J, Ishii T, Iura K, Maekawa A, Bekki H, Ito T, Otsuka H, Kuroda M, Honda Y, Sumiyoshi S, Inoue T, Kinoshita N, Nishida A, Yamashita K, Ito I, Komune S, Taguchi T, Iwamoto Y, Oda Y
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Journal Title
Virchows Archiv
Volume: 470
Pages: 373-380
DOI
Related Report
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[Journal Article] Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene: report of 2 infantile cases and review of the differential diagnosis of infantile pulmonary lesions.2017
Author(s)
Tanaka M, Kohashi K, Kushitani K, Yoshida M, Kurihara S, Kawashima M, Ueda Y, Souzaki R, Kinoshita Y, Oda Y, Takeshima Y, Hiyama E, Taguchi T, Tanaka Y.
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Journal Title
Hum Pathol
Volume: 66
Pages: 177-182
DOI
Related Report
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[Presentation] 固形腫瘍の切除度評価はいつ・誰が・どのように行うべきか? 神経芽腫の外科療法について 切除度の評価について2020
Author(s)
宗崎 良太, 菱木 知郎, 米田 光宏, 小野 滋, 伊勢 一哉, 上原 秀一郎, 風間 理郎, 渕本 康史, 北河 徳彦, 文野 誠久, 高間 勇一, 横井 暁子, 中田 光政, 黒田 達夫, 田尻 達郎, JCCG神経芽腫委員会(JNBSG)外科療法委員会
Organizer
第62回日本小児血液・がん学会
Related Report
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