Combination therapy of molecular targeted drugs and gene therapy for invasive brain tumors and elucidation of the tumor microenvironment
Project/Area Number |
20K09325
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
藤井 謙太郎 岡山大学, 医歯薬学総合研究科, 助教 (40799318)
安原 隆雄 岡山大学, 医歯薬学総合研究科, 准教授 (50457214)
島津 洋介 岡山大学, 医学部, 客員研究員 (90854084)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 分子標的薬 / 遺伝子治療 / 悪性脳腫瘍 / 腫瘍溶解ウイルス / アデノウイルス / 浸潤性モデル / 脳腫瘍 / PDXモデル / CCNファミリー / 浸潤 / 腫瘍微小環境 |
Outline of Research at the Start |
分子標的薬(bevacizumabやPD-1阻害剤)と遺伝子治療(腫瘍溶解ウイルス(OV)またはAd-SGE-REIC)との併用療法の組み合わせについて比較する。分子標的薬と遺伝子治療との併用療法の微小環境変化の比較、治療バイオマーカとの関連実験を行う。さらには再発悪性神経膠腫に対するAd-SGE-REICの医師主導治験から得られた関連因子についての検討を行う。分子標的薬と遺伝子治療との併用療法は浸潤性脳腫瘍治療に対する有効な治療ストラテジーであり、そのCCNファミリーなど腫瘍微小環境の変化に注目することは、治療の新たな展開に必要であると考える。
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Outline of Final Research Achievements |
Malignant brain tumors are an extremely poor prognosis, and Gene therapy and molecular-targeted drugs are promising treatments. In this study, we investigated the combination therapy of molecular-targeted drugs and gene therapy for invasive brain tumors and the involvement of tumor microenvironment-related factors such as the CCN family. In a collaborative study with Okayama University, we focused on tumor microenvironment-related factors such as the CCN family. We found that differentiated glioma cells (DGCs) accelerate tumor progression by making the tumor microenvironment via CCN1-mediated macrophage infiltration. Moreover, we performed TK/GCV suicide gene cell therapy using deciduous tooth pulp stem cells (SHED) and confirmed tumor tropism and antitumor effect. In addition, preliminary OV experiments are underway for oncolytic virus (OV) experiments. In the future, we plan to perform combination therapy.
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Academic Significance and Societal Importance of the Research Achievements |
浸潤性脳腫瘍に対する分子標的薬と遺伝子治療との併用療法とCCNファミリーなどの腫瘍微小環境関連因子の関与については再現性のある結果がえられた。腫瘍微小環境の変化を理解することは腫瘍進展のメカニズムを解明することとなる。また、脱落乳歯歯髄幹細胞(SHED)を用いたTK/GCV自殺遺伝子細胞治療、腫瘍溶解ウイルス療法、分子標的薬と遺伝子治療との併用において、新たな治療法が確立されれば、世界的にもbreakthrough となる悪性脳腫瘍の研究となる。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth2023
Author(s)
Horikawa M, Koizumi S, Oishi T, Yamamoto T, Ikeno M, Ito M, Yamasaki T, Amano S, Sameshima T, Mitani Y, Otani Y, Yan Y, Suzuki T, Namba H, Kurozumi K
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Journal Title
Cancer Gene Therapy
Volume: 30
Issue: 1
Pages: 85-95
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Pyogenic Ventriculitis After Anterior Skull Base Surgery Treated With Endoscopic Ventricular Irrigation And Reconstruction Using a Vascularized Flap2021
Author(s)
Tomita Y , Shimazu Y , Kawakami M , Matsumoto H , Fujii K , Kameda M , Yasuhara T , Suruga Y , Ota T , Kimata Y , Kurozumi K , Date I
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Journal Title
Acta Medica Okayama
Volume: 75
Issue: 2
Pages: 243-248
DOI
NAID
URL
Related Report
Peer Reviewed / Open Access
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[Journal Article] Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration2021
Author(s)
Uneda A, Kurozumi K, Fujimura A, Fujii K, Ishida J, Shimazu Y, Otani Y, Tomita Y, Hattori Y, Matsumoto Y, Tsuboi N, Makino K, Hirano S, Kamiya A, Date I.
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Journal Title
Acta Neuropathol Commun.
Volume: 9
Issue: 1
Pages: 29-29
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detailed arterial anatomy and its anatomoses of the sphenoid ridge and olfactory groove meningiomas with special reference to the recurrent branches from the ophthalmic artery2020
Author(s)
Hiramatsu M , Sugiu K , Hishikawa T , Haruma J , Takahashi Y , Murai S , Nishi K , Yamaoka Y , Shimazu Y , Fujii K , Kameda M , Kurozumi K , Date I
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Journal Title
AJNR Americal Journal of Neuroradiology
Volume: 41(11)
Issue: 11
Pages: 2082-2087
DOI
Related Report
Peer Reviewed
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[Journal Article] Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma2020
Author(s)
Matsumoto Y , Ichikawa T , Kurozumi K , Otani Y , Fujimura A , Fujii K , Tomita Y , Hattori Y , Uneda A , Tsuboi N , Kaneda K , Makino K , Date I
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Journal Title
Acta Neuropathologica Communications
Volume: ー
Issue: 1
Pages: 42-42
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth transduced with herpes simplex virus thymidine kinase2022
Author(s)
Makoto Horikawa, Shinichiro Koizumi, Tomoya Oishi, Taisuke Yamamoto, Masashi Ikeno, Masahiko Ito, Tomohiro Yamasaki, Shinji Amano, Tetsuro Sameshima, Tetsuro Suzuki, Hiroki Namba, Kazuhiko Kurozumi
Organizer
WFNO 2022 Seoul
Related Report
Int'l Joint Research
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