Analysis of human NKT cells and the development of exvivo expansion methods

• Project/Area Number: 14570291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: National Cancer Center Research Institute
• Principal Investigator: WAKASUGI Hiro NCCRI, Pharmacology Division, Chief, 薬効試験部, 部長 (10112632)
• Co-Investigator(Kenkyū-buntansha): IKARASHI Yoshinori NCCRI, Pharmacology Division, Research Associate, 薬効試験部, 研究員 (70280782)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: V_α24^+NKT / α-GalCer / G-CSF / IL-2 / IL-4 / CD1d非拘束性細胞障害 / ヒトNKT細胞 / 対外増殖法 / 自己血漿 / CD1d非拘束性 / CTL / NK細胞 / NKT細胞 / G-CSF投与 / Vα24^+NKT細胞 / ヒト血清・血漿 / 抗腫瘍活性

Research Abstract

Efficient expansion of V_α24^+NKT (V_α24^+CD3^+) cells from granulocyte colony-stimulating factor(G-CSF)-mobilized peripheral blood(PB) cells is possible under culture conditions with α-GalCer, IL-2 and fetal bovine serum(FBS) in vitro^6. In an attempt to avoid potential risks associated with FBS and to establish a clinical-scale expansion system, we investigated the development of a more efficient non-FBS expansion system for V_α24^+ NKT cells with α-GalCer and IL-2.

Research Products

• [Journal Article] The mouse natural killer T cell-associated antigen recognaized by U5A2-13 monoclonal antibody is intercellular adhesion molecule-1 (2004)
  • Author(s): A.Shimizu, et al.
  • Journal Title: Immunology Letters 92 Pages: 227-235
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IL-4 Confers NK Stimulatory Capacity to Murine Dendritic Cells : A Signaling Pathway Involving KARAP/DAP12-Triggering Receptor Express on Myeloid Cell 2 Molecules^1 (2004)
  • Author(s): M.Terme, et al.
  • Journal Title: J.Immunol. 172 Pages: 5957-5966
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The mouse natural killer T cell-associated antigen recognaized by U5A2-13 monoclonal antibody is intercellular adhesion molecule-1 (2004)
  • Author(s): Shimizu, A., Sasaki, H., Aoyagi., Yoshida, M., Kato, K., Heike, Y., Ikarashi, Y., Shirakawa, K., Takaue, Y., Miyajima, A., Terada, M., Nagai, H., Wakasugi, H.
  • Journal Title: Immunology Letters 92 Pages: 227-235
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IL-4 Confers NK Stimulatory Capacity to Murine Dendritic Cells : A Signaling Pathway Involving KARAP/DAP12-Triggering Receptor Express on Myeloid Cell 2 Molecules^1 (2004)
  • Author(s): Terme M, Tomasello E, Maruyama K, Crepineau F, Chaput N, FlamentC, Marolleau JP, Angevin E, Wagner EF, Salomon B, Lemonnier FA, Wakasugi H, Colonna M, Vivier E, Zitvogel L.
  • Journal Title: J.Immunol. 172(10) Pages: 5957-5966
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. (2004)
  • Author(s): Borg C, Terme M, Taieb J, Menard C, Flament C, Robert C, Maruyama K, Wakasugi H, Angevin E, Thielemans K, Le Cesne A, Chung-Scott V, Lazar V, Tchou I, Crepineau F, Lemoine F, Bernard J, Fletcher JA, Turhan A, Blay JY, Spatz A, Emile JF, Heinrich MC, Mecheri S, Tursz T, Zitvogel L.
  • Journal Title: J Clin Invest. 114(3) Pages: 379-388
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NK cell activation by Dendritic Cells (DC)require The Formation of a Synapse leading to IL-12 Polarization in DC. (2004)
  • Author(s): Borg C, Terme M, Taieb J, Menard C, Flament C, Robert C, Maruyama K, Wakasugi H, Angevin E, Thielemans K, Le Cesne A, Chung-Scott V, Lazar V, Tchou I, Crepineau F, Lemoine F, Bernard J, Fletcher JA, Turhan A, Blay JY, Spatz A, Emile JF, Heinrich MC, Mecheri S, Tursz T, Zitvogel L.
  • Journal Title: J Clin Invest. 114(3) Pages: 379-388
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role Of Natural Killer T Cells In Anti-Tumor Immune Response. (2004)
  • Author(s): Yoshinori Ikarashi, Yuji Heike, Atsushi Shimizu, Osamu Imataki, Sachiyo Kanai, Mitsuzi Yoshida, Akira liduka, Takayuki Morikawa, Yoichi Takauel, Hiro Wakasugi.
  • Journal Title: Extended Abstracts for the 34nd International Symposium of the Princess Takamatsu Cancer Research Fund, Tokyo, 2004.
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Allogeneic Immune-Mediated Anti-Cancer Effect With Reduced-Intensity Stem Cell Transplantation. (2004)
  • Author(s): Yuji Heike, Masahiro Kami, Shinichiro Mori, Ryuji Tanosaki, Shigesaburo Miyakoshi, Shuichi Taniguchi, Hiro Wakasugi, Yoichi Takaue.
  • Journal Title: Extended Abstracts for the 34nd International Symposium of the Princess Takamatsu Cancer Research Fund, Tokyo, 2004.
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased expansion of Vα24^+ T cells derived from G-CSF mobilized peripheral blood stem cells as compared to peripheral blood mononuclear cells following α-galactosylceramide stimulation. (2003)
  • Author(s): R.Asada-Mikami, et al.
  • Journal Title: Cancer Science 94 Pages: 383-388
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] U5A2-13, an antigen originally found on mouse NK-like T Cells, is an early inducible cell surface antigen during lymphoid activation. (2003)
  • Author(s): K.Katoh, et al.
  • Journal Title: Cellular immunology 221 Pages: 27-36
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CD4^+ CD25^+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. (2003)
  • Author(s): H.Nishikawa, et al.
  • Journal Title: Proc Natl Acad Sci USA 100 Pages: 10902-10906
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Increased expansion of V_24^+T cells derived from G-CSF mobilized peripheral blood stem cells as compared to peripheral blood mononuclear cells following_-galactosylceramide stimulation. (2003)
  • Author(s): Rumiko Asada-Mikami, Yuji Heike, Yukie Harada, Sachiyo Kanai, Yoshinori Ikarashi, Kazunori Kato, Kazuo Shirakawa, Yoichi Takaue, Tatsuo Abe, Hiro Wakasugi.
  • Journal Title: Cnacer Science 94 Pages: 383-388
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] U5A2-13, an antigen originally found on mouse NK-like T Cells, is an early inducible cell surface antigen during lymphoid activation. (2003)
  • Author(s): Kazunori Kato, Yoshinori Ikarashi, Toshiaki Sugahara, Atsushi Yasumoto, David Sancho, Mitsuzi Yoshida, Yoichi Takaue, Yoshiro Kobayashi, Francisco Sanchez-Madrid, Hiro Wakasugi.
  • Journal Title: Cellular Immunology 221 Pages: 27-36
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CD4^+ CD25^+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. (2003)
  • Author(s): Hiroyoshi Nishikawa, Takuma Kato, Koji Tanida, Atsunori Hiasa, Isao Tawara, Hiroaki Ikeda, Yoshinori Ikarashi, Hiro Wakasugi, Mitchell Kronenberg, Toshinori Nakayama, Masaru Taniguchi, Kagemasa Kuribayashi, Lloyd J.Old, Hiroshi Shiku.
  • Journal Title: Proc Natl Acad Sci USA 100 Pages: 10902-10906
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] U1B3.3 monoclonal antibody recognizes a precursor of NK1.1+ cytotoxic T cells generated by interleukin-2 (2002)
  • Author(s): Y.Ikarashi, et al.
  • Journal Title: Proceedings of the Japan Academy 78 Pages: 91-95
  • NAID: 130000907847
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] U1B3.3 monoclonal antibody recognizes a precursor of NK1.1^+ cytotoxic T cells generated by interleukin-2. (2002)
  • Author(s): Ikarashi Y, Kato K, Yoshida M, Wakasugi H.
  • Journal Title: Proc.Japan Acad. 78 Pages: 91-95
  • NAID: 130000907847
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Role Of Natural Killer T Cells In Anti-Tumor Immune Response. (2004)
  • Author(s): Y.Ikarashi, et al.
  • Publisher: Princes Takamatsu Cancer Research Fund
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Rumiko Asada-Mikami, et al.: "Increased expansion of Vα24' T cells derived from G-CSF mobilized peripheral blood stem cells as compared to peripheral blood mononuclear cells following α-galactosylceramide stimulation."Cnacer Science. 94. 383-388 (2003)
• [Publications] Kazunori Kato, et al.: "U5A2-13, an antigen originally found on mouse NK-like T Cells, is an early inducible cell surface antigen during lymphoid activation."Cellular Immunology. 221. 27-36 (2003)
• [Publications] Hideyuki Ishida, et al.: "Determining the Levels of Matrix Metalloproteinase-9 in Portal and Peripheral Blood is Useful for Predicting Liver Metastasis of Colorectal Cancer."Jpn J Clin Oncol. 33. 186-191 (2003)
• [Publications] Mitsuzi Yoshida, et al.: "Involvement of PKC beta II in Anti-Proliferating Action of a New Antitumor Compound Gnidimacrin."Int.J.Cancer. 105. 601-606 (2003)
• [Publications] Kunihisa Nakai, et al.: "Anti-thymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution."Transplantation. 75. 2135-2143 (2003)
• [Publications] Sachie Matsuda, et al.: "Separation of Phospholipids and Glycolipids Using Analytical Toroidal-Coil Counter-Current Chromatography. α. Comparison of the Hydrophobicity Between Mycoplasma fermentans and Human-Brain Lipids."Journal of Liquid Chromatography & Related Technologies. 26. 1135-1147 (2003)
• [Publications] Kazuo Shirakawa: "Hemodynamics in Vasculogenic Mimicry and Angiogenesis of Inflammatory Breast Cancer Xenograft"Cancer Res.. 62. 560-566 (2002)
• [Publications] Hisataka Kobayashi: "Rapid Accumulation and Internalization of Radiolabeled Herceptin in an Inflammatory Breast Cancer Xenograft with Vasculogenic Mimicry Predicted by the Contrast-enhanced Dynamic MRI with the Macromolecular Contrast Agent G6-(1B4M-Gd)"Cancer Res.. 62. 860-866 (2002)
• [Publications] Kazuo Shirakawa: "Tumor-Infiltrating Endothelial Cells and Endothelial Precursor Cells in Inflammatory Breast Cancer"Int. J. Cancer. 99. 344-351 (2002)
• [Publications] Takeshi Saito: "Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma"Clin. Cancer Res. 8. 1014-1020 (2002)
• [Publications] Yoshinori Ikarashi: "U1B3.3 monoclonal antibody recognizes a precursor of NK1.1^+ cytotoxic T cells generated by interleukin-2"Proc. Japan Acad.. 78. 91-95 (2002)
• [Publications] Kazuo Shirakawa: "Vasculogenic Mimicry and Pseudo Comedo Formation in Breast Cancer"Int. J. Cancer. 99. 821-828 (2002)
• [Publications] Je-Jung Lee: "The Role of PGE_2 in the Differentiation of Dendritic Cells : How Do Dendritic Cells Influence T-Cell Polarization and Chemokine Receptor Expression?"STEM CELLS. 20. 448-459 (2002)
• [Publications] Kazuo Shirakawa: "Induction of vasculogenesis in breast cancer models"Br. J. Cancer. 87. 1454-1461 (2002)
• [Publications] Kazunori kato: "U5A2-13 : An Antigen Originally Found on Mouse NK-like T Cells, Is An Early Inducible Cell Surface Antigen During Lymphoid Activation"Cellular Immunology. (in press). (2003)
• [Publications] Kunihisa Nakai: "Anti-thymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution"Transplantation. (in press). (2003)
• [Publications] Rumiko-Asada-Mikami: "Increased expression of Vα24^+ T cells derived from G-CSF mobilized peripheral blood stem cells as compared to peripheral blood mononuclear cells following α-galactsylceramide stimulation"Cancer Science. (in press). (2003)
• [Publications] Kazuo Shirakawa: "Vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model"Breast cancer Research. (in press). (2003)