Study on the Usefulness of the Novel Tumor Marker MK-1 in the Diagnosis and Therapy of Cancer

• Project/Area Number: 20590593
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Fukuoka University
• Principal Investigator: KUROKI Masahide Fukuoka University, 医学部, 教授 (40122692)
• Co-Investigator(Renkei-kenkyūsha): SHIBAGUCHI Hirotomo 福岡大学, 医学部, 講師 (60295061) ; TANAKA Toshihiro 福岡大学, 医学部, 講師 (00398314)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 癌 / 免疫学 / バイオテクノロジー / モノクローナル抗体 / MK-1

Research Abstract

Using the ELISA for MK-1, we found that MK-1 is useful for some malignant tumors. A human monoclonal anti-MK-1 antibody, M13-57, revealed antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity against MK-1-expressing cells, suggesting that this antibody may be useful for antibody-based therapy of cancer. Also, a chimeric T-cell antigen receptor consisting of M13-57 scFv, CD28 and CD3 ζ induced a wild-type T-cell receptor-like molecular event upon MK-1 binding, suggesting that this may be useful for cancer therapy.

Research Products

• [Journal Article] CEA特異的なヒト単鎖型抗体遺伝子のクローニングとキメラT細胞受容の作製 (2011)
  • Author(s): 白須直人,芝口浩智,黒木求,山田博美,黒木政秀
  • Journal Title: 日本分子腫瘍マーカー研究会誌 26 Pages: 26-27
• [Journal Article] Amphiregulin regulates the activation of ERK and Akt through EGFR and HER3 signals involved in the progression of pancreatic cancer. (2010)
  • Author(s): Yotsumoto F., Fukami T., Yagi H., Funakosi A., Yoshizato T., Kuroki Ma, Miyamoto S.
  • Journal Title: Cancer Sci. 101(11) Pages: 2351-2360
  • Peer Reviewed
• [Journal Article] HB-EGF orchestrates the signals involved in triple-negative and trastuzumab-resistant breast cancer. (2010)
  • Author(s): Yotsumoto F., Oki E., Tokunaga E., Maehara Y., Kuroki Ma., Hiroto Mizushima H., Mekada E., Miyamoto S.
  • Journal Title: Int.J.Cancer 127(11) Pages: 2707-2717
  • Peer Reviewed
• [Journal Article] Construction and molecular characterization of human chimeric T cell antigen receptors specific for carcinoembryonic antigen. (2010)
  • Author(s): Shirasu N., 芝口浩智, Kuroki Mo., Yamada H., Kuroki Ma.
  • Journal Title: Anticancer Res. 30(7) Pages: 2731-2738
  • Peer Reviewed
• [Journal Article] HB-EGF orchestrates the signals illvolved in triple-negative and trastuzumab-resistant breast cancer (2010)
  • Author(s): Yotsumoto, F., Oki, E., Tokunaga, E., Maehara, Y., Kuroki, Ma., et al.
  • Journal Title: International Journal of Cancer Volume: 127 Pages: 2707-2717
  • Peer Reviewed
• [Journal Article] Amphiregulin regulates the activation of ERK and Akt through EGFR and HER3 signals involved in the progression of pancreatic cancer (2010)
  • Author(s): Yotsumoto, F., Fukami, T., Yagi, H., Funakosi, A., Yoshizato, T., Kuroki, Ma., et al.
  • Journal Title: Cancer Science Volume: 101 Pages: 2351-2360
  • Peer Reviewed
• [Journal Article] Emerging strategies for ErbB ligand-based targeted the rapy for cancer (2010)
  • Author(s): Tsujioka, H., Yotsumoto, F., Shirota, K., Horiuchi, S., Yoshizato, T., Kuroki, Ma., et al.
  • Journal Title: Anticancer Research Volume: 30 Pages: 3107-3112
  • Peer Reviewed
• [Journal Article] Recent developments in cancer gene therapy with adenovirus vectors. (2009)
  • Author(s): Tanaka T., Shibaguchi H., Maekawa S., Shimura H., Tamura K., Kuroki Ma.
  • Journal Title: Trends Cancer Res. 5(1) Pages: 63-69
• [Journal Article] Engineering T cells in cancer immunotherapy : strategy for gene construction and antitumor activity. (2009)
  • Author(s): Shibaguchi H., Tanaka T., Luo N., Kuroki Ma.
  • Journal Title: Trends Cancer Res. 5(1) Pages: 21-27
• [Journal Article] FU-MK-1 expression in human gallbladder carcinoma : An antigenic prediction marker for a better postsurgical prognosis. (2009)
  • Author(s): Ikeda T., Nakayama Y., Hamada Y., Takeshita M., Iwasaki H., Maeshiro K., Yamashita Y., Kuroki Ma., Ikeda S.
  • Journal Title: Am.J.Clin.Pathol. 132(1) Pages: 111-117
  • Peer Reviewed
• [Journal Article] Amphiregulin regulates the production of human chorionic gonadotropin in trophoblasts. (2009)
  • Author(s): Fukami T, Yoshizato T, Miyamoto S, Yagi H, Yotsumoto F, Nabeshima K, Hachisuga T, Kuroki Ma, Kawarabayashi T
  • Journal Title: Life Sci. 84(23-24) Pages: 796-804
  • Peer Reviewed
• [Journal Article] Claudin-1 protein is a major factor involved in the tumorigenesis of colorectal cancer. (2009)
  • Author(s): Huo Q., Kinugasa T., Wang L., Huang J., Shibaguchi H, Kuroki Mo., Tanaka T., Yamashita Y., Nabeshima K., Iwasaki H, Kuroki Ma
  • Journal Title: Anticancer Res. 29(3) Pages: 851-857
  • Peer Reviewed
• [Journal Article] Synergistic anti-tumor effect of paclitaxel with CRM197, an inhibitor HB-EGF, in ovarian cancer. (2009)
  • Author(s): Yagi H., Yotsumoto F., Sonoda K., Kuroki Ma., Mekada E., Miyamoto S.
  • Journal Title: Int.J.Cancer 124(6) Pages: 1429-1439
  • Peer Reviewed
• [Journal Article] FU-MK-1 expression in human gallbladder carcinoma : Anantigenic prediction marker for a better postsurgical prognosis (2009)
  • Author(s): Ikeda, T., Nakayama, Y., Hamada, Y., et al.
  • Journal Title: Am.J.Clin.Pathol. 132 Pages: 111-117
  • Peer Reviewed
• [Journal Article] Amphiregulin regulates the production of human chorionic gonadotropin in trophoblasts (2009)
  • Author(s): Fukami, T., Yoshizato, T., Miyamoto, S., et al.
  • Journal Title: Life Sci. 84 Pages: 796-804
  • Peer Reviewed
• [Journal Article] Claudin-1 protein is a major factor involved in the tumori-genesis of colorectal cancer (2009)
  • Author(s): Huo, Q., Kinugasa, T., Wang, L., et al.
  • Journal Title: Anticancer Res. 29 Pages: 851-857
  • Peer Reviewed
• [Journal Article] Synergistic anti -tumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer (2009)
  • Author(s): Yaei, H., Yotsumoto, F., Sonoda, K., Kurok i, M., et al.
  • Journal Title: Int. J. Cancer 124 Pages: 1429-1439
  • Peer Reviewed
• [Journal Article] Recombinant human monoclonal IgA antibody against CEA to recruit neutrophils to CEA-expressing cells. (2008)
  • Author(s): Zhao J., Kuroki Mo., Shibaguchi H., Wang L., Huo Q., Takami N., Tanaka T., Kinugasa T., Kuroki Ma.
  • Journal Title: Oncol.Res. 17 Pages: 217-222
  • Peer Reviewed
• [Journal Article] Tumor targeting carboxylesterase fused with anti CEA scFv improve the anticancer effect with a less toxic dose of irinotecan. (2008)
  • Author(s): Uchino J., Takayama K., Harada A., Sone T., Harada T., Curiel D.T., Kuroki Ma., Nakanishi Y.
  • Journal Title: Cancer Gene Ther. 15 Pages: 94-100
  • Peer Reviewed
• [Journal Article] Tumor targeting carboxylesterase fused with anti CEA scFv improve the anticancer effect with a less tox ic dose of irinotecan (2008)
  • Author(s): Uchino, J., Takayama, K., Harada, A., et al.
  • Journal Title: Cancer Gene Ther. 15 Pages: 94-100
  • Peer Reviewed
• [Journal Article] Recombinant human monoclonal IgA antibody against CEA to recruit neutrophils to CEA -expressing cells (2008)
  • Author(s): Zhao, J., Kuroki, Mo., Shibaguchi, H., et al.
  • Journal Title: Oncol. Res. 17 Pages: 217-222
  • Peer Reviewed
• [Presentation] Secreted production of bifunctional sc-Fv antibody-based fusion protein of IL-2 and FU-MK-1(VH-Vκ)in Pichia pastoris. (2011)
  • Author(s): Anuleechan, S., Palaga, T., Kuroki, Mo., Kuroki, Ma., Chanprateep, S.
  • Organizer: Nano in Cancer : Linking Chemistry, Biology, and Clinical Applications In Vivo
  • Place of Presentation: マイアミ (アメリカ)
  • Year and Date: 2011-01-14
• [Presentation] Production of bifunctional sc-Fv antibody-based fusion proteins of IL-2/FU-MK-1(VH-Vκ) and IL-2/FU-MK-1(Vκ-VH) in Escherichia coli, Nano in Cancer : Linking Chemistry, Biology, and Clinical Applications In Vivo (2011)
  • Author(s): Chanprateep S., Kongchanasombat M., Pohthisoong N., Kuroki Mo., Kuroki Ma.
  • Place of Presentation: Miami, Florida
• [Presentation] Secreted production of bifunctional sc-Fv antibody-based fusion protein of IL-2 and FU-MK-1(VH-VK) in Pichia pastoris, Nano in Cancer : Linking Chemistry, Biology, and Clinical Applications In Vivo (2011)
  • Author(s): Anuleechan S., Palaga T., Kuroki Mo., Kuroki Ma., Chanprateep S.
  • Place of Presentation: Miami, Florida
• [Presentation] Identification of genes regulating of HB-EGF as a target for breast cancer therapy. (2010)
  • Author(s): Yotsumoto F., Kuroki Ma., Miyamoto S.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Construction and functional analyaia of human chimeric T cell antigen receptors specific for carcinoembryonic antigen. (2010)
  • Author(s): Shirasu N., Shibaguchi H., Kuroki Mo., Yamada H., Kuroki Ma.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Development of molecularly targeted against HB-EGF for proteins with ovarian cancer. (2010)
  • Author(s): Miyamoto S., Yotsumoto F., Kuroki Ma.
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Enhancement of antitumor activity in the combination therapy of anticancer dug and a fully human antibody specific for CEA is involved in CDC and ADCC, but not anoikis. (2010)
  • Author(s): Shibaguchi H., Tsuru H., Kuroki Mo., Kuroki Ma.
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: Kobe (Japan)
• [Presentation] Hyperactive glycoprotein B mutations augment fully retargeted HSV infection. (2010)
  • Author(s): Uchida H., Chan J., Nakano K., Kwon H., Goins W.F., Kumagai I., Kurok, Ma., Grandi P., Cohen J.B., Glorioso J.C.
  • Organizer: The 35th International Herpesvirus Workshop
  • Place of Presentation: Salt Lake City, Utah, USA
• [Presentation] Heparin-binding epidermal growth factor-like growth factor as a target molecule for triple negative breast cancer therapy (2009)
  • Author(s): Yotsumoto, F., Oki, E., Tokunaga, E., et al.
  • Organizer: 37th Meeting of the International Society of Oncology and BioMarkers(ISOBM)
  • Place of Presentation: オランダ
  • Year and Date: 2009-09-29
• [Presentation] HB-EGF as a target molecule for triple negative breast cancer therapy. (2009)
  • Author(s): Yotsumoto F., Oki E., Tokunaga E., Maehara Y., Sanui A., Fukami T., Kuroki Ma., Mizushima H., Mekada E., Miyamoto S.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Heparin-binding epidermal growth factor-like growth factor as a target molecule for triple negative breast cancer therapy. (2009)
  • Author(s): Yotsumoto F., Oki E., Tokunaga E., Maehara Y., Sanui A., Fukami T., Kuroki Ma., Mizushima H., Mekada E., Miyamoto S.
  • Organizer: 37th Meeting of the International Society of Oncology and BioMarkers (ISOBM)
  • Place of Presentation: Amsterdam (The Netherlands)(Oral)
• [Presentation] Phase I study of BK-UK (CRM197) in patients with ovarian cancer (2008)
  • Author(s): Miyamoto, S., Yotsu moto, F., Fukami, T., et al.
  • Organizer: 36th Meeting of the International Society of Oncology and BiolMarkers
  • Place of Presentation: 東京
  • Year and Date: 2008-10-06
• [Presentation] Combination therapy of gastric cancer using a human antibody to CEA and anticancer drugs. (2008)
  • Author(s): Shibaguchi H., Tsuru H., Kuroki Mo., Tanaka T., Kuroki Ma.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] The validation of CRM197, a specific inhibitor for HB-EGF, for molecularly targeted in breast cancer patients. (2008)
  • Author(s): Yotsumoto F., Oki E., Tokunaga E., Maehara Y., Kuroki Ma., Mizushima H., Mekada E., Miyamoto S.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Efficacy of cross-reacting material 197 (CRM197), a specific inhibitor for heparin-bindingepidermal growth factor-like growth factor (HB), in breast cancer patients. (2008)
  • Author(s): Yotsumoto F., Oki E., Tokunaga E., Maehara Y., Kuroki Ma., Mizushima H., Mekada E., Miyamoto S.
  • Organizer: 36th Meeting of the International Society of Oncology and BioMarkers (ISOBM)
  • Place of Presentation: Tokyo (Japan)
• [Presentation] Phase I study of BK-UK (CRM197) in patients with ovarian cancer. (2008)
  • Author(s): Miyamoto S., Yotsumoto F., Fukami T., Sanui A., Kuroki Ma., Mekada E.
  • Organizer: 36th Meeting of the International Society of Oncology and BiolMarkers (ISOBM)
  • Place of Presentation: Tokyo (Japan)
• [Presentation] Heparin-binding epidermal growth factor-like growth factor (HB) regulates mammary tumorigenesis through EGFR as well as Her2 signal. (2008)
  • Author(s): Yotsumoto F., Yagi H., Fukami T., Kuroki Ma., Mizushima H., Mekada E., Miyamoto S.
  • Organizer: 99th Annual Meeting of the American Association for Cancer Research (AACR)
  • Place of Presentation: San Diego (USA)
• [Presentation] Synergistic anti-tumor effects in combination of Gemcitabine with inhibitors for amphiregulin. (2008)
  • Author(s): Fukami T., Yagi H., Yotsumoto F., Funakoshi A., Kuroki Ma., Mekada E., Miyamoto S.
  • Organizer: 99th Annual Meeting of the American Association for Cancer Research (AACR)
  • Place of Presentation: San Diego (USA)
• [Book] Peptide Science 2009.(K.Okamoto, ed.)(Characteristic difference of biological activity between Arg-containing and Lys-containing peptide.) (2010)
  • Author(s): Mizoe Y., Shioi N., Terada S., Uchida Y., Kuroki Ma., Lee S.
  • Publisher: The Japanese Peptide Society Fukuoka
• [Book] Peptide Science 2009 (2010)
  • Author(s): Mizoe, Y., Shioi, N., Terada, S., Uchida, Y., Kuroki, M, Lee, S.
  • Total Pages: 491
  • Publisher: The Japanese Peptide Society(Osaka)
• [Book] Methods in Molecular Biology(U.Reineke and M.Schutkowski, eds.)(Vol.524, Epitope Mapping Protocols, A solid-phase mutual inhibition assay with labeled antigen.) (2009)
  • Author(s): Kuroki Ma.
  • Publisher: Humana Press Totowa NJ
• [Book] Methods in Molecular Biology (2009)
  • Author(s): Kuroki, Ma.
  • Total Pages: 7
  • Publisher: Humana Press
• [Book] Methods in Molecular Biology (2009)
  • Author(s): Kuroki, M.
  • Total Pages: 426
  • Publisher: Humana Press
• [Book] Recent Developments in Immunology(J.Xiang, ed.)(Fusion therapy of cellular and humoral immunity for cancer using antibodies or their genes against carcinoembryonic antigen.) (2008)
  • Author(s): Kuroki Ma., Wang L., Huo Q., Shibaguchi H., Yanagisawa J., Fukami T., Yotsumoto F., Tanaka T., Miyamoto S.
  • Publisher: Transworld Research Network Kerala India
• [Remarks]
  • URL: http://www.med.fukuoka-u.ac.jp/biochem1/index-j.htm