遺伝子およびドラッグデリバリーシステムのがん臨床応用をめざす研究

2009 年度 研究成果報告書

• 研究課題/領域番号: 17016087
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 国立がんセンター(研究所及び東病院臨床開発センター)
• 研究代表者: 松村 保広 国立がんセンター(研究所及び東病院臨床開発センター), がん治療開発部, 部長 (90209619)
• 研究分担者: 眞鍋 史乃 (60300901)
• 研究期間 (年度): 2005 – 2009
• キーワード: ナノ材料 / 分子認識 / 医療・福祉 / 癌 / 薬理学

研究概要

ミセル製剤はEPR効果により、腫瘍集積性に富み、種々の抗がん剤を安定的にミセル内包化できる。ミセルのサイズは20から100nmの範囲に制御できる。よってミセルは正常血管からは漏れず、副作用を減少できる。種々のミセル製剤につき、前臨床試験を行い、その結果をもとに、臨床治験が行われている。次に、我々は腫瘍間質に対する抗体を作成し、その抗体に抗がん剤を付加した複合体を作成した。この複合体は投与後、血管透過性に富む腫瘍血管から選択的に漏出し、腫瘍間質に集積後、そこを足場として、徐放的に時間依存性の抗がん剤を放出し、効率的にがん細胞および腫瘍血管に到達して、高い抗腫瘍効果を発揮するというCAST(Cancer Stromal Targeting)療法を提唱した。

研究成果

• [雑誌論文] Antitumor Effect of NK012, SN-38 Incorporating Polymeric Micelle on U87MG Orthotopic Glioblastoma in Mice Compared with Irinotecan in Combination with Bevacizumab. (2010)
  • 著者名/発表者名: J Kuroda, Y Matsumura, et al.
  • 雑誌名: Clin Cancer Res. 16(2) ページ: 521-9
• [雑誌論文] Synergistic Antitumor Activity of the SN-38-Incorporating Polymeric Micelles NK012 with S-1 in a Mouse Model of Non-Small Cell Lung Cancer. (2010)
  • 著者名/発表者名: T Nagano, Y Matsumura, et al.
  • 雑誌名: Int J Cancer. (in press.)
• [雑誌論文] The antitumor activity of NK012, a SN-38 incorporating micelle, in combination with bevacizumab against lung cancer xenografts. (2010)
  • 著者名/発表者名: H Kenmotsu, Y Matsumura, et al.
  • 雑誌名: Cancer. (in press)
• [雑誌論文] Potent antitumor effect of SN-38-incorporating polymeric micelle, NK012, against malignant glioma. (2009)
  • 著者名/発表者名: J Kuroda, Y Matsumura, et al.
  • 雑誌名: Int J Cancer. 124 ページ: 2505-2511
• [雑誌論文] Preclinical and clinical studies of anticancer agent-incorporating polymer micelles. (2009)
  • 著者名/発表者名: Y Matsumura, K Kataoka.
  • 雑誌名: Cancer Sci. 100 ページ: 572-579
• [雑誌論文] Antitumor activity of NK012 combined with cisplatin against small-cell lung cancer and intestinal mucosal changes in tumor-bearing mouse after treatment. (2009)
  • 著者名/発表者名: T Nagano, Y Matsumura, et al.
  • 雑誌名: Clin Cancer Res 15(13) ページ: 4348-4355
• [雑誌論文] NK012. (2009)
  • 著者名/発表者名: Y Matsumura.
  • 雑誌名: Drugs of the Future. (Thomson Reuters) 34(4) ページ: 276-281
• [雑誌論文] Antitumour activity of NK012, SN-38-Incorporating Polymeric Micelles, in Hypovascular Orthotopic Pancreatic Tumour. (2009)
  • 著者名/発表者名: Y Saito, Y Matsumura, et al.
  • 雑誌名: Eur J Cancer 46 ページ: 650-658
• [雑誌論文] Syneragistic antitumor activity of the novel SN-38 incorporating polymeric micelles, NK012, combined with 5-fluorouracil in a mouse model of colorectal cancer, as compared with that of irinotecan plus 5-fluorouracil. (2008)
  • 著者名/発表者名: T Nakajima, Y Matsumura, et al.
  • 雑誌名: Int J Cancer. 122 ページ: 2148-2153
• [雑誌論文] Enhanced distribution of NK012 and prolonged sustained-release of SN-38 within tumors are the key strategic point for a hypovascular tumor. (2008)
  • 著者名/発表者名: Y Saito, Y Matsumura, et al.
  • 雑誌名: Cancer Sci 99;6 ページ: 1258-1264
• [雑誌論文] Novel SN-38-incorporated polymeric micelles, NK012, strongly suppress renal cancer progression. (2008)
  • 著者名/発表者名: M Sumitomo, Y Matsumura, et al.
  • 雑誌名: Cancer Res. 68(6) ページ: 1631-1635
• [雑誌論文] Poly (amino acid) micelle nanocarriers in preclinical and clinical studies. (2008)
  • 著者名/発表者名: Y Matsumura.
  • 雑誌名: In Advanced Drug Delivery Reviews (eds. VHL Lee, MK Forrest, and GS Kwon)(Elsevier B.V.V.) 60/8 ページ: 899-914
• [雑誌論文] Antitumor effect of SN-38-releasing polymeric micelles, NK012, on spontaneous peritoneal metastases from orthotopic gastric cancer in mice compared with irinotecan. (2008)
  • 著者名/発表者名: Nakajima-Eguchi T, Y Matsumura, et al.
  • 雑誌名: Cancer Res. 68(22) ページ: 9318-9322
• [雑誌論文] Tumor specific ultrasound enhanced gene transfer in vivo with novel liposomal bubbles. (2008)
  • 著者名/発表者名: R Suzuki, Y Matsumura, et al.
  • 雑誌名: Journal of controlled release. 125 ページ: 137-144
• [雑誌論文] Polymeric micellar delivery systems in Oncology. (2008)
  • 著者名/発表者名: Y Matsumura.
  • 雑誌名: Jpn J Clin Oncol. 38(12) ページ: 793-802
• [雑誌論文] A Phase I and Pharmacokinetic Study of NK105, a Paclitaxel-incorporating Micellar Nanoparticle Formulation. (2007)
  • 著者名/発表者名: T Hamaguchi, Y Matsumura, et al.
  • 雑誌名: Brit J Cancer. 97 ページ: 170-176
• [雑誌論文] Preclinical and clinical studies of anticancer drug-incorporated polymeric micelles. (2007)
  • 著者名/発表者名: Y Matsumura.
  • 雑誌名: J Drug Targeting 15(7-8) ページ: 507-517
• [雑誌論文] NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitizing agent compared to free paclitaxel. (2006)
  • 著者名/発表者名: T Negishi, Y Matsumura, et al.
  • 雑誌名: Brit J Cancer. 95 ページ: 601-606
• [雑誌論文] Novel SN-38-incorporated polymeric micelles, NK012, eradicate vascular endothelial growth factor-secreting bulky tumors. (2006)
  • 著者名/発表者名: F Koizumi, Y Matsumura, et al.
  • 雑誌名: Cancer Res 66 ページ: 10048-10056
• [雑誌論文] Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-Triggered Drug Release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. (2005)
  • 著者名/発表者名: Y Bae, Y Matsumura, et al.
  • 雑誌名: Bioconjugate Chem. 16 ページ: 122-130
• [雑誌論文] NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel. (2005)
  • 著者名/発表者名: T Hamaguchi, Y Matsumura, et al.
  • 雑誌名: Brit J Cancer. 92 ページ: 1240-1246
• [雑誌論文] Cisplatin-Incorporating Polymeric Micelles (NC-6004) Can Reduce Nephrotoxicity and Neurotoxicity of Cisplatin in Rats. (2005)
  • 著者名/発表者名: H Uchino, Y Matsumura, et al.
  • 雑誌名: Brit J Cancer. 93 ページ: 678-687
• [学会発表] Anticancer agents-incorporated micelle carrier systems under clinical evaluation. (2009)
  • 著者名/発表者名: Y Matsumura
  • 学会等名: The 14th International Symposium on Recent Advances in Drug Delivery Systems.
  • 発表場所: Salt Lake City, Utah, USA.
  • 年月日: 20090215-20090218
• [学会発表] Drug Delivery System. (2008)
  • 著者名/発表者名: Y Mastumura
  • 学会等名: The 18th HCS International Symposium Recent Progress in Pathogenesis and Management of Colorectal Cancer International Conference Center.
  • 発表場所: Hiroshima, Japan.
  • 年月日: 20081100
• [学会発表] A preclinical, clinical, and translational study on micelle carrier system in oncology. (2008)
  • 著者名/発表者名: Y. Matsumura
  • 学会等名: 6th International Nanomedicine and Drug Delivery Symposium.
  • 発表場所: Toronto, Canada.
  • 年月日: 20081000
• [学会発表] NK012, a polymeric micelle formation containing SN-38, markedly enhanced the antitumor activity of SN-38 against orthotopic glioblastoma multiforme tumors in a mouse model. (2008)
  • 著者名/発表者名: J. Kuroda, M. Yasunaga, J. Kuratsu, Y. Matsumura.
  • 学会等名: AACR Annual Meeting 2008.
  • 年月日: 20080412-20080416
• [学会発表] Clinical Development of Polymer Therapeutics in Japan. (2008)
  • 著者名/発表者名: Y. Matsumura.
  • 学会等名: 7th International Symposium on Polymer Therapeutics from Laboratory to Clinical Practice 27th.
  • 発表場所: Valencia, Spain
  • 年月日: 2008-05-27
• [学会発表] Comparative study of new immuno-magnetic beads for isolation of exfoliated cells from feces as a non-invasive method for diagnosing colorectal cancer (2008)
  • 著者名/発表者名: Y. Koga, M. Yasunaga, H. Baba, Y. Matsumura.
  • 学会等名: 2008 AACR Annual Meeting
  • 発表場所: San Diego
  • 年月日: 2008-04-13
• [学会発表] AACR Annual Meeting2008. Importance of enhanced distribution of NK012 and long-term, sustained-release of SN-38 for the treatment of hypovascular tumors. (2008)
  • 著者名/発表者名: Yohei Saito, Masahiro Yasunaga, Junichiro Kuroda, Yoshikatsu Koga, Yasuhiro Matsumura.
  • 学会等名: 2008 AACR Annual Meeting
  • 発表場所: San Diego
  • 年月日: 2008-04-13
• [学会発表] Local gene delivery combined with ultrasound and bubble-liposome against superficial bladder cancer. (2008)
  • 著者名/発表者名: Suguru Fujisawa, Yasuhiro Matsumura
  • 学会等名: 2008 AACR Annual Meeting
  • 発表場所: San Diego
  • 年月日: 2008-04-13
• [学会発表] Micelle carrier system in cancer chemotherapy. (2007)
  • 著者名/発表者名: Y. Matsumura.
  • 学会等名: 9th US-Japan DDS symposium.
  • 発表場所: Maui.
  • 年月日: 20071216-20071220
• [学会発表] Novel SN-38-incorporating polymeric micelles, NK012, eradicate vascular endothelial growth factor-secreting bulky tumors (2007)
  • 著者名/発表者名: F. Koizumi, Y. Matsumura.
  • 学会等名: 98th AACR Annual meeting
  • 年月日: 20070414-20070418
• [学会発表] Arterial infusion of nucleic acids through rat carotid artery as an experimental local gene delivery system: Looking ahead to future clinical trials. Los Angels Convention Center. Los Angels Convention Center. (2007)
  • 著者名/発表者名: J. Kuroda, J. Kuratsu, Y. Matsumura.
  • 学会等名: AACR Annual Meeting 2007.
  • 年月日: 20070414-20070418
• [学会発表] Polymeric micellar delivery systems in preclinical and clinical and trials. (2007)
  • 著者名/発表者名: Y. Matsumura.
  • 学会等名: 38th International symposium of the princess Takamatsu cancer research fund.
  • 発表場所: Tokyo.
  • 年月日: 2007-11-29
• [学会発表] Improved isolation of exfoliated cells from feces for noninvasive diagnosis of colorectal cancer: A comparative study of new immuno-magnetic beads. (2007)
  • 著者名/発表者名: Y. Koga, H. Matsushita, M. Yasunaga, H. Baba, Y. Matsumura
  • 学会等名: 2007 AACR Annual Meeting
  • 発表場所: Los Angeles
  • 年月日: 2007-04-15
• [学会発表] Novel SN-38-incorporating polymeric micelles, NK012, eradicate vascular endothelial growth factor-secreting bulky tumors. (2006)
  • 著者名/発表者名: F. Koizumi, Y. Matsumura
  • 学会等名: The Joint Meeting of The 3rd ISC International Conference on Cancer Therapeutics The 11th International Symposium on Cancer Chemotherapy.
  • 発表場所: Tokyo.
  • 年月日: 20061206-20061208
• [学会発表] Experimental Local Gene Delivery System: Looking Ahead to a Future Clinical Trial. (2006)
  • 著者名/発表者名: Y. Matsumura
  • 学会等名: The 1st FIP-APSTJ joint Workshop on Gene Delivery Committee.
  • 発表場所: Sapporo
  • 年月日: 20060709-20060714
• [学会発表] Phase I study of NK105, a paclitaxel-incorporating micellar nanoparticle, in patients with advanced cancer. (2006)
  • 著者名/発表者名: K Kato, T Hamaguchi, H Yasui, T Okusaka, H Ueno, M Ikeda, K Shirao, Y Shimada, H Nakahama, K Muro, Y Matsumura.
  • 学会等名: 2006 ASCO.
  • 発表場所: Atlanta
  • 年月日: 20060602-20060606
• [学会発表] Novel SN-38-incorporated polymeric micelles, NK012 eradicate vascular endothelial growth factor-secreting bulky tumors. (2006)
  • 著者名/発表者名: F. Koizumi, Y. Matsumura
  • 学会等名: 97th AACR
  • 発表場所: Washington.
  • 年月日: 20060330-20060415
• [学会発表] Preclinical and clinical study of NK105, a paclitaxel-incorporating micellar nanoparticle formation. (2005)
  • 著者名/発表者名: Y. Matsumura
  • 学会等名: The 32th Controlled Release Society.
  • 発表場所: Miami.
  • 年月日: 20050618-20050621
• [学会発表] The cytotoxicity and intracellular distributions of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in ovarian cancer cell lines. (2005)
  • 著者名/発表者名: K Shimada, T Kasamatsu, T Hasegawa, Y Kanai, H Niki, T Tagawa, Y Matsumura.
  • 学会等名: 96th AACR
  • 発表場所: Anaheim, California.
  • 年月日: 20050416-20050420
• [産業財産権] 癌間質の構成因子に対して特異的結合能を有する物質と抗腫瘍性化合物との複合体による新規の癌ターゲティング治療 (2008)
  • 発明者名: 松村保広, ら
  • 権利者名: (財)ヒューマンサイエンス振興財団独立行政法人理化学研究所
  • 産業財産権番号: 特願・2008-293930
  • 出願年月日: 2008-11-17
• [産業財産権] 新規な抗フィブリン抗体
  • 発明者名: 松村保広, ら
  • 権利者名: (財)ヒューマンサイエンス振興財団独立行政法人理化学研究所
  • 産業財産権番号: 特願・2010-139572