2001 Fiscal Year Final Research Report Summary
New transcatheter arterial embolization therapy for unresectable hepatocellular carcinoma using ferromagnetic iron-dextran reagents combined with anticancer drug and bispecific antibody
| Project/Area Number |
11470254
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
SUZUKI Masanori Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (70206530)
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| Co-Investigator(Kenkyū-buntansha) |
KATAYOSE Yu Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (20302151)
ENDO Kojin Tohoku University Hospital, Research Associate, 医学部附属病院, 助手 (70292315)
UNNO Michiaki Tohoku University Graduate School of Medicine, Research Associate, 大学院医学系研究科, 助手 (70282043)
OSADA Yukihiro The Institute of Physical and Chemical Research (RIKEN), Chief Investigator, 抗生物質研究室, 主任研究員(研究職) (80160836)
MIURA Shigeto High Field Laboratory for Superconducting Materials, Institute for Materials Research, Tohoku University, Associate Professor, 強磁場超刺激伝導材料研究センター, 助教授 (90005893)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Hepatocellular carcinoma / ferromagnetic iron-dextran / Bispecific antibody |
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| Research Abstract |
With the aim to see the fate of unresectable tumor of the liver, we are planning to embolize the tumor feeding artery via transcatheteric route by novel embolus, ferromagnetic iron-dextran along with Reveromycine (RM) - A, which is a mitogenic inhibitor and bispecific antibody targeting for both hepatoma cells and LAK cells. This complex forms a colloid which will held at tumor site by creating a magnetic field around the tumor site. For the component of novel transcatheteric hepatic arterial embolus, we synthesized two kinds of bispecific antibodies (BsAbs), i.e., (OKXL) BsAbs constructed with both OKT-3 (anti-CD3) and L-7-6 (anti-HCC), and (3GXL) BsAbs constructed with 3-G-8 (anti-CD-16) and L-7-6 antibodies by chemical reconstruction method. The cytotoxicity was tested by MTT assay in several conditions. These two BsAbs, having pairs of binding arms on their single molecule, showed similar binding to target cells as the parental monoclonal antibodies (OKT-3, 3-G-8, L-7-6), when examined with FACS. Newly devised in vitrocytotoxicity tests revealed that LAK or PWM-simulated LAK (PWM-LAK) cells did not show any significant cytotoxic activity to HCC cells, while both effector/target (0.3) in the presence of BsAbs (OKXL) for the efficient retargeting of the effector cells. Inasmuch as PWM-LAK cells proliferate in vitro 3-5 times faster than LAK cells, adoptive immunotherapy using PWM-LAK cells in combination with (OKXL) BsAbs should be very promising.
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[Publications] Kudo T, Suzuki M, Katayose Y, Masao S, Sakurai N, Kodama H, Ichiyama M, Takemura S, Yosida H, Saeki H, Saijyo S, Takahashi J, Tominaga T, Matsuno S: "Specific targeting immunotherapy of cancer with bispecific antibodies"Tonoku J Exp Med. 188. 275-288 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Asano R, Takemura S, Tsumoto K, Sakurai N, Teramae A, Ebara S, Katayose Y, Shinoda M, Suzuki M, Imai K, Matsuno S, Kudo T, Kumagai I: "Functional construction of the anti-mucin core protein (MUCI) antibody MUSE 11variable regions in a bacterial expression system"J. Biochem.. 127. 673-679 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Shinichi Takemura, Ryutaro Asano, Kouhei Tsumoto, Takashi Arai, Naoki Sakurai, Hideaki Kodama, Hiroshi Yoshida, Yu Katayose, Masanori Suzuki, Seiki Matsuno, Toshio Kudo, Izumi Kumagai: "Functional Fv fragment of an antibody specific for CD28 : Fv-mediated co-stimulatiion of T cells"FEBS letters. 476. 266-271 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Shinichi Takemura, Ryutaro Asano, Kouhei Tsumoto, Shinji Ebara, Naoki Sakurai, Yu Katayose, Hideaki Kodama, Hiroshi Yoshida, Masanori Suzuki, Kohzoh Imai, Seiki Matsuno, Toshio Kudo, Izumi Kumagai: "Construction of a diabody (small recombinant bispecific antibody) using a refolding system"Protein Engineering. 13. 583-588 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kudo T, Suzuki M, Takemura S, Asano R, Tumoto K, Katayose Y, Shinoda M, Sakurai N, Kodama H, Ichiyama M, Yoshida H, Hayashi H, Saito S, Takahashi J, Kumagai I: "Second generation bispecific antibodies : An application to cancer immunotherapy"Recent Research Developments in Cancer. 1. 395-402 (2000)
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「研究成果報告書概要(欧文)」より
