Novel chemothemotherapy for brain tumors using a nano-carrier combined with ICG

• Project/Area Number: 16K10750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Chiba University
• Principal Investigator: IWADATE Yasuo 千葉大学, 大学院医学研究院, 教授 (70272309)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: glioma / liposome / nanocarrier / chemotherapy / immune response / HSP70 / 光線力学免疫療法 / グリオーマ / 化学療法 / ICG / ナノキャリア / 光線力学療法 / 脳腫瘍学

Outline of Final Research Achievements

We have developed a liposome combined with indocyanine green (ICG) which specifically accumulates in a brain tumor model and generates heat and active oxygen when irradiated with infrared ray. We planned to use this particle as a nanocarrier enclosed with anticancer agents. A significant reduction in tumor progression was observed in the treated tumors, which was accompanied with a high expression of heat shock protein-70. This efficacy was also accompanied with CD-8 T cell accumulation and not observed in the immuno-compromised animals. However, enclosure of temozolomide did not generate an additional efficacy. It is supposed to be important in the treatment of brain tumors how effectively tie the tumor cell death to the induction of acquired immunity.

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は希少疾患であるが、最も悪性度の高い脳腫瘍であり、50歳代に高頻度に発症するため社会的損失の大きい疾患である。血液脳関門(BBB)の存在により、薬剤移行性が不良でありその治癒を阻む一因となる。我々は、近赤外蛍光色素であるindocianine green (ICG) 結合型リポソームをナノキャリアとして用い、種々の抗がん剤をその中に封入し、腫瘍局所に高濃度に分布させることによって効率的に細胞死を誘導し、特異的抗腫瘍免疫が誘導されることを示した。

Research Products

• [Journal Article] Photo-immune therapy with liposomally formulated phospholipid-conjugated indocyanine green induces specific antitumor responses with heat shock protein-70 expression in a glioblastoma model (2018)
  • Author(s): Shibata Sayaka、Shinozaki Natsuki、Suganami Akiko、Ikegami Shiro、Kinoshita Yuki、Hasegawa Ryozo、Kentaro Hirata、Okamoto Yoshiharu、Aoki Ichio、Tamura Yutaka、Iwadate Yasuo
  • Journal Title: Oncotarget Volume: 10 Issue: 2 Pages: 175-183
  • DOI: 10.18632/oncotarget.26544
  • Peer Reviewed / Open Access
• [Journal Article] Plasticity in Glioma Stem Cell Phenotype and Its Therapeutic Implication (2018)
  • Author(s): Iwadate Y
  • Journal Title: Neurologia medico-chirurgica Volume: 58 Issue: 2 Pages: 61-70
  • DOI: 10.2176/nmc.ra.2017-0089
  • NAID: 130006351483
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed / Open Access
• [Journal Article] The pluripotent stem-cell marker alkaline phosphatase is highly expressed in refractory glioblastoma with DNA hypomethylation. (2017)
  • Author(s): Iwadate, Y., Suganami, A., Tamura, Y., Matsutani, T., Hirono, S., Shinozaki, N., Hiwasa, T., Takiguchi, M., and Saeki, N.
  • Journal Title: Neurosurgery Volume: 80 Issue: 2 Pages: 248-248
  • DOI: 10.1093/neuros/nyw026
  • Peer Reviewed
• [Journal Article] Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction (2017)
  • Author(s): Wang H,Zhang X-M,Tomiyoshi G,Nakamura R,Shinmen N,Kuroda H,Kimura R,Mine S,Kamitsukasa I,Wada T,Aotsuka A,Yoshida Y,Kobayashi E,Matsutani T,Iwadate Y,Sugimoto K,Mori M,Uzawa A,Muto M,Kuwabara S,Takemoto M,Kobayashi K,Kawamura H,Ishibashi R,Yokote K,Ohno M,
  • Journal Title: Oncotarget Volume: 9 Issue: 5 Pages: 5600-5613
  • DOI: 10.18632/oncotarget.23789
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack (2017)
  • Author(s): Yoshida Y, Wang H, Hiwasa T, Machida T, Takiguchi M, Iwadate Y, et al.
  • Journal Title: Oncotarget Volume: 9 Issue: 3 Pages: 8836-8848
  • DOI: 10.1007/s11060-018-2831-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular imaging of 1p/19q deletion in oligodendroglial tumor with 11C-Methionine positron emission tomography. (2016)
  • Author(s): Iwadate Y, Shinozaki N (Co-first), Matsutani T, Uchino Y, Saeki N.
  • Journal Title: J Neurl Neurosurg Psy Volume: 印刷中 Issue: 9 Pages: 1016-1021
  • DOI: 10.1136/jnnp-2015-311516
  • Peer Reviewed / Open Access
• [Journal Article] Transforming growth factor-β and stem cell markers are highly expressed around necrotic areas in glioblastoma. (2016)
  • Author(s): Iwadate Y, Matsutani T, Hirono S, Shinozaki N, Saeki N.
  • Journal Title: J Neurooncol Volume: 129 Issue: 1 Pages: 101-107
  • DOI: 10.1007/s11060-016-2145-6
  • Peer Reviewed
• [Journal Article] Epithelial-mesenchymal transition in glioblastoma progression (2016)
  • Author(s): Iwadate Y
  • Journal Title: Oncol Lett Volume: 11 Issue: 3 Pages: 1615-1620
  • DOI: 10.3892/ol.2016.4113
  • Peer Reviewed
• [Presentation] グリオーマにおけるDNA低メチル化に伴う幹細胞マーカー発現 (2017)
  • Author(s): 岩立康男、松谷智郎、池上史郎、廣野誠一郎、小林正芳、原彩佳、菅波晃子、田村裕
  • Organizer: 日本脳神経外科学会
• [Presentation] 膠芽腫の悪性転化ー低酸素環境によるDNA脱メチル化 (2016)
  • Author(s): 岩立康男、松谷智郎、原 彩佳、篠崎夏樹、菅波晃子、田村 裕
  • Organizer: 第75回日本脳神経外科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2016-09-29