2001 Fiscal Year Final Research Report Summary
Therapeutic strategy for hepatocellular carcinoma by dendritic cell-based tumor vaccination
| Project/Area Number |
12557054
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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 | 展開研究 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
HAYASHI Norio Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00144478)
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| Co-Investigator(Kenkyū-buntansha) |
OKAWA Kazuyoshi Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
HIRAMATSU Naoki Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
SASAKI Yutaka Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70235282)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Tumor vaccine / Hepatocellular carcinoma / Dendritic cell / Immunogene therapy / Interleukin 12 |
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| Research Abstract |
Dendritic cells (DC) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combined effectiveness of tumor lysate-pulsed DC immunization and interleukin-12 (IL-12) administration on the induction of antitumor immunity in mouse hepatocellular carcinoma (HCC) model. Mouse DC were pulsed with lysate of BNL 1MB A.7R.1(BNL), a BALB/c-derived HCC cell line, and then injected into syngeneic mice in combination with systemic administration of IL-12. Lymphocytes from mice treated with BNL lysate-pulsed DC and IL-12 showed stronger cytolytic activity and produced higher amounts of IFNγ than those from mice treated with BNL lysate-pulsed DC alone. Although immunization with BNL lysate-pulsed DC alone did not lead to complete regression of established tumors, it significantly inhibited tumor growth compared with vehicle injection. Importantly, the combined therapy of BNL lysate-pulsed DC and IL-12 resulted in tumor rejection or significant inhibition of tumor growth compared with mice treated with BNL lysate-pulsed DC alone. In vivo lymphocyte depletion experiments demonstrated that this combination was dependent on both CD8^+ and CD4^+ T cells, but not NK cells. These results demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DC against HCC in mice. This combination of IL-12 and DC may be useful for suppressing growth of residual tumor after primary therapy of human HCC.
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[Publications] Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, Hayashi N.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II"J Virol. 74. 1241-1251 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Kato M, Masuzawa M, Oshita M, Naito M, Kashiwagi T, Yoshihara H, Hori M, Kamada T.: "Pretreatment viral load and response to interferon therapy for liver cirrhosis caused by hepatitis C virus : a multicenter controlled study"Hepatol Res. 16. 124-133 (2000)
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[Publications] Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Sasaki Y, Kakumu S, Kiyosawa K, Okita K, Osaka Liver Disease Study Group: "Clinical characteristics of patients with chronic hepatitis C showing biochemical remission, without hepatitis C virus eradication, as a result of interferon therapy"J Viral Hep. 7. 343-351 (2000)
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[Publications] Tanaka H, Tsukuma H, Kasahara A, Hayashi N, Yoshihara H, Masuzawa M, Kanda T, Kashiwagi T, Inoue A, Kato M, Oshita A, Kinoshita Y, Kamada T.: "Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C : A retrospective cohort study of 738 patients"Int J Cancer. 87. 741-749 (2000)
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[Publications] Horimoto M, Sasaki Y, Ugawa S, Wada S, Toyama T, Iyoda K, Yakushijin T, Minami Y, Ito T, Hijioka T, Eguchi A, Nakanishi M, Shimada S, Tohyama M, Hayashi N, Hori M.: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer"Cancer Gene Ther. 7. 1341-1347 (2000)
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[Publications] Katayama K, Kasahara A, Sasaki Y, Kashiwagi T, Naito M, Masuzawa M, Katoh M, Yoshihara H. Kamada T. Mukuda T, Hijioka T, Hori M, Hayashi N.: "Immunological response to interferon-γ priming prior to interferon-α treatment in refractory chronic hepatitis C in relation to viral clearance"J Viral Hep. 8. 180-185 (2001)
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[Publications] Tatsumi T, Takehara T, Kanto T, Miyagi T, Kuzushita N, Sugimoto Y, Jinushi M, Kasahara A, Sasaki Y, Hori M, Hayashi N.: "Administration of interleukin 12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma"Cancer Res. 61. 7563-7567 (2001)
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