Development of the anti-tumor DDS based on novel tumor-homing peptides

2011 Fiscal Year Final Research Report

• Project/Area Number: 21200078
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry; Applied pharmacology
• Research Institution: 愛知県がんセンター研究所 (2011); Aichi Cancer Center Research Institute (2009-2010)
• Principal Investigator: KONDO Eisaku 愛知県がんセンター研究所, 腫瘍病理学部, 部長 (30252951)
• Co-Investigator(Kenkyū-buntansha): SAITO Ken (70426584)
• Co-Investigator(Renkei-kenkyūsha): MATSUSHITA Masayuki (30273965)
• Project Period (FY): 2009 – 2011
• Keywords: 分子腫瘍学 / ドラッグデリバリー

Research Abstract

We developed novel tumor linegae-homing CPPs that are highly permeable to cancer cells according to their tumor linages. Random peptide library constructed by mRNA display technology was employed for isolating the CPPs encoded by novel aminoacid sequences which differ from conventional CPPs such as TAT,pAnt. Screening of over 40 CPPs of these,10 of them showed unique response that were efficiently incorporated to tumor cells following their tumor origins. These tumor linage-homing CPPs were efficiently incorporated to target cells in vivo and in vitro and are useful in peptide-based non-invasive medical technologies such as anti-cancer therapeutics and imaging.

Research Products

• [Journal Article] Tumour lineage-homing cell-penetrating peptides for peptide-based anti-cancer molecular delivery systems. (※ correspondence ; Kondo E and Matsushita M) (2012)
  • Author(s): Kondo E, Saito K, Tashiro Y, Kamide K, Uno S, Furuya T, Mashita M, Nakajima K, Tsumuraya T, Kobayashi N, Nishibori M, Tanimoto M, Matsushita M
  • Journal Title: Nature Communications Volume: (in press)
  • Peer Reviewed
• [Journal Article] Establishment and characterization of novel gastric signet-ring cell and non signet-ring cell, poorly-differentiated adenocarcinoma cell lines with low and high malignant potential (2012)
  • Author(s): Murakami, H., Nakanishi, H., Tanaka, H., Ito, S., Misawa, K., Ito, Y., Ikehara, Y., Kondo, E., Kodera, Y
  • Journal Title: Gastric Cancer Volume: (Epubahead of print)
  • Peer Reviewed
• [Journal Article] TGF-b synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth (2012)
  • Author(s): Fujii, M., Toyoda, T., Nakanishi, H., Yatabe, Y., Sato, A., Matsudaira, Y., Ito, H., Murakami, H., Kondo, Y., Kondo, E., Hida, T., Tsujimura, T., Osada, H., Sekido, Y.
  • Journal Title: J. Exp. Med. Volume: 209(3) Pages: 479-94
  • Peer Reviewed
• [Journal Article] Acquisition of EMT phenotype in the gefitinib-resistant cells of a head and neck squamous cell carcinoma cell line through Akt/GSK-3β/snail signaling pathway (2012)
  • Author(s): Maseki, S., Ijichi, K., Tanaka, H., Fujii, M., Hasegawa, Y., Ogawa T, Murakami, S., Kondo, E., Nakanishi, H.
  • Journal Title: Br. J. Cancer Volume: 106(6) Pages: 1196-20
  • Peer Reviewed
• [Journal Article] MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6 (2011)
  • Author(s): Saito K, Kondo E and Matsushita M.
  • Journal Title: Nuc. Acid Res. Volume: 39(14) Pages: 6086-6099
  • Peer Reviewed
• [Journal Article] NFATc1 affects mouse splenic B cell function by controlling the calcineurin. NFAT signaling network (2011)
  • Author(s): Bhattacharyya S, Deb J, Patra AK, Thuy Pham DA, Chen W, Vaeth M, Berberich-Siebelt F, Klein-Hessling S, Lamperti ED, Reifenberg K, Jellusova J, Schweizer A, Nitschke L, Leich E, Rosenwald A, Brunner C, Engelmann S, Bommhardt U, Avots A, Muller MR, Kondo E, Edgar Serfling
  • Journal Title: J. Exp. Med. Volume: 208(4) Pages: 823-39
  • Peer Reviewed
• [Journal Article] miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg.. (2011)
  • Author(s): Yamamoto M, Kondo E, Takeuchi M, Harashima A, Otani T, Tsuji-Takayama K, Yamasaki F, Kumon H, Kibata M, Nakamura S.
  • Journal Title: PLoS One. Volume: 6(2) Pages: e16841
  • Peer Reviewed
• [Journal Article] Potent anti-tumor killing activity of the multifunctional Treg cell line HOZOT against human tumors with diverse origins (2011)
  • Author(s): Inoue T, Tashiro Y, Takeuchi M, Otani T, Tsuji-Takayama K, Okochi A, Mukae Y, Koreishi M, Yamasaki F, Kumon H, Nakamura S, Kibata M, Kondo E.
  • Journal Title: Int. J. Oncol. Volume: 38(5) Pages: 1299-1306
  • Peer Reviewed
• [Journal Article] Treatment of acute liver failure in mice by hepatocyte xenotransplantation (2010)
  • Author(s): Yamamoto T, Navarro-Alvarez N, Soto-Gutierrez A, Yuasa T, Iwamuro M, Kubota Y, Seita M, Kawamoto H, Javed SM, Kondo E, Noguchi H, Kobayashi S, Nakaji S, Kobayashi N.
  • Journal Title: Cell Transplant Volume: 19 Pages: 799-806
  • Peer Reviewed
• [Journal Article] Critical role of Pcid2 in B cell survival through the regulation of MAD2 expression (2010)
  • Author(s): Nakaya T, Kuwahara K, Ohta K, Kitabatake M, Toda T, Takeda N, Tani T, Kondo E, Sakaguchi N.
  • Journal Title: J. Immunol Volume: 185 Pages: 5180-5187
  • Peer Reviewed
• [Journal Article] Hepatic differentiation of mouse iPS cells in vitro (2010)
  • Author(s): Iwamuro M, Komaki T, Kubota Y, Seita M, Kawamoto H, Yuasa T, Javed SM, Hassan RARA, Nakaji S, Nishikawa Y, Kondo E, Yamamoto K, Fox IJ, Kobayashi N
  • Journal Title: CellTransplantation Volume: 19 Pages: 841-847
  • Peer Reviewed
• [Journal Article] Comparative analysis of endoderm formation efficiency between mouse EScellsand iPS cells. (2010)
  • Author(s): Iwamuro M, Komaki T, Kubota Y, Seita M, Kawamoto H, Yuasa T, Javed SM, Hassan RARA, Nakaji S, Nishikawa Y, Kondo E, Yamamoto K, Kobayashi N
  • Journal Title: Cell Transplantation Volume: 19 Pages: 831-839
  • Peer Reviewed
• [Journal Article] Targeted delivery of oligomannose-coated liposome to the omental micrometastasis by peritoneal macrophages from patients with gastric cancer (2010)
  • Author(s): Matsui M, Shimizu, Y Ikehara Y, Kondo E, Kodera Y, Nakanishi H.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1670-1677
  • Peer Reviewed
• [Journal Article] Characteristics of CD133(+) human colon cancer SW620 cells (2010)
  • Author(s): Kawamoto H, Yuasa T, Kubota Y, Seita M, Sasamoto H, Javed SM, Hayashi T, Nakahara H, Hassan R, Iwamuro M, Kondo E, Nakaji S, Tanaka N, Kobayashi N
  • Journal Title: CellTransplantation Volume: 19 Pages: 857-864
  • Peer Reviewed
• [Journal Article] Isolation andpropagation of a human CD133-negative colon tumor-derived cell line withtumorigenic and angiogenic properties (2010)
  • Author(s): Navarro-Alvarez N, Kondo E, Soto-gutierrez A, Kawamoto H, Hassan W, Yuasa T, Kubota Y, Seita M, Nakahara H, Hayashi T, Nishikawa Y, Hassan RARA, JavedSM, Noguchi H, Matsumoto S, Nakaji S, Tanaka N, Kobayashi N
  • Journal Title: Cell Transplantation Volume: 19 Pages: 865-877
  • Peer Reviewed
• [Presentation] Nanobiotechnology using novel CPPs for anti-tumor medicine (2011)
  • Author(s): Kondo E.
  • Organizer: BioJapan 2011
  • Place of Presentation: 横浜
  • Year and Date: 2011-10-07
• [Presentation] In vitro and in vivo analysis of anti-tumor activity of multifunctional T cell line, HOZOT (2011)
  • Author(s): Inoue T, Otani T, Tsuji-Takayama K, Takeuchi M, Kondo E, Nakamura S
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Development of highly efficient cell-pepnetrating peptides for anti-tumor medicine (2011)
  • Author(s): Kondo E
  • Organizer: 第70回日本癌学会学術総会(セミナー)
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Identification of key effector in gefitinib response NSCLC (2011)
  • Author(s): Saito K, Kondo E, Nakanishi H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Development of tumor lineage-homing peptides for molecular delivery systems in anti-cancer medicin (2011)
  • Author(s): Kondo E, Saito K, Nakanishi H
  • Organizer: 第70回日本癌学会学術総会(シンポジウム)
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 固形がん細胞増殖抑制の標的分子候補としてのCAR(CXADR)の解析 (2011)
  • Author(s): 近藤英作
  • Organizer: 第15回日本がん分子標的治療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-23
• [Presentation] 細胞膜透過性ペプチドの応用による制がん技術展開へのアプローチ (2011)
  • Author(s): 近藤英作
  • Organizer: 第27回日本DDS学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-09
• [Presentation] 悪性腫瘍における新規増殖制御因子OGFOD-1の機能の解析 (2011)
  • Author(s): 斎藤憲, 中西速夫, 近藤英作
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-29
• [Presentation] 口腔がんにおけるアデノウイルスレセプターCAR が果たす増殖制御の役割 (2011)
  • Author(s): 近藤英作, 小屋恵理子, 斉藤憲, 中西速夫
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-29
• [Presentation] ゲフィティニブ耐性肺がんの機能性ペプチド導入による新しい増殖制御法の検討 (2011)
  • Author(s): 近藤英作, 小屋恵理子, 斉藤憲, 中西速夫
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-28
• [Presentation] Development of novel cancer cell-selective cell-penetrating peptides for the advanced peptide-based drug delivery system (2010)
  • Author(s): Kondo, E.
  • Organizer: 22nd EORTC-NCI-AACR Symposium
  • Place of Presentation: Berlin
  • Year and Date: 2010-11-18
• [Presentation] がん細胞選択的高透過性ペプチドを応用した抗腫瘍ペプチドデリバリー系の開発 (2010)
  • Author(s): 近藤英作, 中西速夫, 松井誠, 冨田勇樹
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] アデノウイルス受容体(CAR;CXADR)の固形癌細胞の増殖制御における役割の解析 (2010)
  • Author(s): 小屋恵理子, 阪口政清, 松井誠, 冨田勇樹, 許南浩, 近藤英作
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] 分子標的ツールとしてのがん選択的細胞膜浸潤性を発揮する新規高透過能ペプチドの開発研究 (2010)
  • Author(s): 近藤英作
  • Organizer: 第14回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-07
• [Presentation] ヒト各種悪性腫瘍細胞におけるCXADR 分子の発現の特徴とその生物学的役割についての解析 (2010)
  • Author(s): 松井誠, 中西速夫, 近藤英作
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-29
• [Presentation] (2009)
  • Author(s): 近藤英作
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20091000
• [Presentation] 胚中心におけるRelファミリー転写因子の発現と役割 (2009)
  • Author(s): 近藤英作
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-05-02
• [Presentation] Experimental Approach for Growth Inhibition of Human Malignancies by the Highly Efficient Anti-tumor Peptides Delivery System (2009)
  • Author(s): Eisaku Kondo
  • Organizer: CTS-JSOPMB Joint Conference
  • Place of Presentation: Okayama
  • Year and Date: 2009-04-21
• [Presentation] Experimental Approach for Growth Inhibition of Human Malignancies by the Highly Efficient Transporter-mediated Anti-tumor Peptide Delivery System (2009)
  • Author(s): Eisaku Kondo
  • Organizer: The 2nd Annual Protein and Peptide Conference (PepCon-2009)
  • Place of Presentation: Seoul
  • Year and Date: 2009-04-04
• [Book] 「細胞膜透過ペプチドを応用した医療技術展開へのアプローチ」遺伝子医学MOOK 21号「最新ペプチド合成技術とその創薬研究への応用」 (2012)
  • Author(s): 近藤英作, 中島喜一郎
  • Total Pages: 179-183
  • Publisher: メディカルドウ社
• [Remarks] 研究内容・成果に関するホームページ
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/02shuyo_byori/index.html
• [Patent(Industrial Property Rights)] 癌細胞選択的膜透過性ペプチドおよびその利用 (2010)
  • Inventor(s): 近藤英作, 松下正之
  • Industrial Property Rights Holder: 愛知県, 三菱化学
  • Industrial Property Number: 特願2010-088186, PCT出願 PCT/JP2011/058616
  • Filing Date: 2010-04-06
  • Acquisition Date: 2010-04-05