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A STUDY ON IMMUNOTHERAPY OF ORAL CANCERS

Research Project

Project/Area Number 04404077
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 外科・放射線系歯学
Research InstitutionTOKYO MEDICAL AND DENTAL UNIVERSITY

Principal Investigator

FUJIBAYASHI Takashi  Tokyo Medical and Dental University, The Second Dept.of Oral & Maxillofacial Surgery, Associate Professor, 歯学部, 助教授 (80013978)

Co-Investigator(Kenkyū-buntansha) AZUMA Miyuki  Juntendou University, Department of Immunology, Resaerch Associate, 医学部, 助手 (90255654)
KAMATA Nobuyuki  Same with the above institution and department, Research Associate, 歯学部, 助手 (70242211)
ISHII Masatoshi  Same with the above institution and department, Research Associate, 歯学部, 助手 (70212826)
TAKAHASHI Yuzo  Tokyo Medical and Dental University, The Second Dept.of Oral & Maxillofacial Sur, 歯学部, 講師 (50014329)
杉山 芳樹  東京医科歯科大学, 歯学部, 助手 (00162909)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1992: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsoral cancer / OK-432 / LAK cells / adoptive immunotherapy / chemotherapeutic agents / co-stimulatory signal / CD80 / CD86 / LAK療法 / 免疫能 / costimulatory分子 / CD28 / 化学療法剤処理 / サイトカイン / B7 / BB1 / B70 / IL-2(インターロイキン2) / 養子兔疫療法 / OK-432 / 主要組織適合抗原 / TIL(腫瘍組織浸潤リンパ球) / 化学療法
Research Abstract

Cell-mediated immunity of oral cancer patients in terms of peripheral blood lymphocytes, CD3^+, CD4^+, CD8^+, CD4/CD8 ratio, and so on were compared between patients with tumor recurrence and patients without recurrence. Tumor recurrence group showed significant decrease in cell-mediate immunity. Then, Thirty-one oral cancer patients who received immunotherapy by OK-432 were examined and compared with 23 control patients who received no immunotherapy. Decrease of CD3^+ cells and CD4^+ cells due to cancer treatments was inhibited by OK-432 immuno-therapy, and inhibitory effect on decrease of NK activity during cancer treatments was also recognized in the immunotherapy group. Not only single BRM therapy such as OK-432 but also the therapeutic efficacy of adoptive immunotherapy with the adoptive transfer of autologous LAK cells plus recombinant interleukin-2 (rlL-2) activated with anti-CD3 monoclonal antibody and rlL-2 was investigated in oral cancer patients. Although cytotoxic activity … More of single CD3/LAK cells induced by solid phase anti-CD3 monoclonal antibody plus rlL-2 showed lower than that of LAK cells activated by single rlL-2, total lytic activity of whole culture of CD3/LAK cells showed greater because of vigorous proliferation of CD3/LAK cells.
To improve the therapeutic efficacy of adoptive immunotherapy by CD3/LAK cells, the effect of the combination therapy of CD3/LAK and chemo-therapy or administration of other cytokines was investigated. Pretreatments of target cultured cell lines established from oral cancer cells with chemotherapeutic agents such as CDDP,5-FU increased cytotoxic activity of CD3/LAK cells. In contrast, pretreatments of the target cells with IFN-gamma, TNF-alpha decreased the cytotoxic activity of CD3/LAK cells. By combination of pretreatment of IFN-gamma and CDDP or 5-FU the decrease of the cytotoxic activity of CD3/LAK cells by IFN-gamma was reduced in resulting compensation of the cytotoxic activity.
Recent immunological studies have revealed that both specific ligand and co-stimulatory signals such as CD28 on T cells and CD80, CD86 on APC are required for the induction, activation and clonal expansion from naive T cells to active CTL.Although active B cells, macrophages, and professional APC such as dendolitic cells were expressing CD80, CD86, almost all tumor cells showed no expression of them. The experimental animal model of CD80 gene transfection to CD80 negative mice fibrosarcoma cell line (Meth A) showed rejection of growth of Meth A in syngenic mice. The immunologic specificity of Meth A specific rejection indicted that tumor specific CTL is induced by this gene therapy. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] 藤林孝司、後藤聡、高橋雄三、森 良之、湊 秀次、榎本昭二: "口腔領域悪性腫瘍患者再発症例の細胞性免疫能に関する研究" Biotherapy. 7. 150-157 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 藤林孝司、後藤聡、高橋雄三、森 良之、湊 秀次、榎本昭二: "口腔領域悪性腫瘍患者の細胞性免疫能に対するOK-432の効果" Biotherapy. 7. 158-166 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshiyuki Mori and Yuzo Takahashi: "Studies on induction of antitumorcy to toxicity on tumol infiltrating lynphocytes of patients with oral malignant tumors." Dentistry in Japan. 30. 80-86 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 湊 秀次、高橋雄三、上條達夫、森 良之、東みゆき、藤林孝司ほか: "化学療法剤処理口腔扁平上皮癌由来細胞株のLAK感受性と細胞膜抗原" 日本口腔外科学会雑誌. 39. 1477-1478 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyuki Azuma,Daisuke Ito,Hideo Yagita et al.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 東 みゆき: "リンパ球活性化機序ーCostimulatory分子によるT細胞機能発現の調節ー" 日本臨床免疫学会誌. 17. 654-660 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takashi Fujibayashi, Satoshi Gotoh, Yuzo Takahashi, Yoshiyuki Mori, Syuji Minato and Shoji Enomoto: "Cell-mediated immunity in recurrent malignant tumors of the oral cavity." Biotherapy. 7. 150-157 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takashi Fujibayashi, Satoshi Gotoh, Yuzo Takahashi, Yoshiyuki Mori, Syuji Minato and Shoji Enomoto: "Effectiveness of OK-432 for cell-mediated immunity in malignant tumors of the oral cavity." Biotherapy. 7. 158-166 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshiyuki Mori and Yuzo Takahashi: "Studies on induction of antitumor cytotoxicity on tumor infiltrating lymphocytes of patients with oral malignant tumors." Dentistry in Japan. 30. 80-86 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Syuji Minato, Yuzo Takahashi, Tatsuo Kamizyo, Yoshiyuki Mori, Miyuki Azuma, Takashi Fujibayashi and Shoji Enomoto: "LAK sensitivity and cell membrane antigens of chemotherapeutic agents treated cultured cell lines derived from oral squamous cell cancers." Jap.J.Oral Maxillofac.Surg.39. 1477-1478 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyuki Azuma, Daisuke Ito, Hideo Yagita, Ko Okumura, Joseph H.Phillips, Lewis L.Lanier and Chamorro Somoza: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyuki Azuma: "Mechanism of T cell activation ; control of expression of T cell function by co-stimulatory molecules." Jap.J.Clin.Immunol.17. 654-660 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shuji Minato et al.: "Adoptive Immunotherapy for Oral Cancer Patients using Lympbokine-activated killer Cells(LAK)" 35th Am.Meeting Scientific Sessions of Korean A cad.Orale Max.-Fac.Surg. Abstract Book. 128-128 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 湊秀次、ほか: "口腔癌治療のLAK養子免疫療法併用による免疫学的検査値の変動" 第13回日本口腔腫瘍学会抄録集. 55-55 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 東 みゆき: "リンパ球活性化機序-Costimulatory分子によるT細胞機能発現の調節-" 日本臨床免疫学会会誌. 17. 654-660 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 八木田秀雄、東みゆき、ほか: "腫瘍特異的CTLの誘導とその遺伝子治療への応用" 実験医学. 12. 1898-1904 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 東みゆき、ほか: "2つのCD28/CTLA-4 リガンド、CD80(B7)とCD86(B70)の機能および発現の相違(1)" 日本免疫学会総会・学術集会記録. 24. 464-464 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 瀬戸口靖弘、東みゆき、ほか: "アデノウイルスベクターによるCD80遺伝子導入と腫瘍特異的CTLの誘導" Biotherapy. 9. 27-33 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 藤林孝司ら: "口腔領域悪性腫瘍患者再発症例の細胞性免疫能に関する研究" Biotherapy. 7. 150-157 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 藤林孝司ら: "口腔領域悪性腫瘍患者の細胞性免疫能に対するOK-432の効果" Biotherapy. 7. 158-166 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshiyuki Mori and Yuzo Takahashi: "Studies on induction of antitumor cytotoxicity on tumor infiltrating lymphocytes of patients with oral malignant tumors." Dentistry in Japan. 30. 80-86 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 湊 秀次 ほか: "化学療法剤処理口腔扁平上皮癌由来細胞株のLAK感受性と細胞膜抗原" 第38回日本口腔外科学会総会抄録集. 193-193 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Miyuki Azuma,et al.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Miyuki Azuma,et al.: "Requirements for CD28-dependent T cell-mediated cytotoxicity." J.Immunol.150. 2091-2101 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森 良之: "口腔扁平上皮癌患者リンパ球より誘導された抗CD3抗体/IL-2活性化細胞(CD3・LAK)の標的細胞認識の検索" 頭頸部腫瘍. 18. 120-124 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 藤林 孝司: "口腔領域悪性腫瘍患者再発症例の細胞性兔疫能に関する研究" Biotherapy. 7. 150-157 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 藤林 孝司: "口腔領域悪性腫瘍患者の細胞性免疫能に対するCK-432の効果" Biotherapy. 7. 158-166 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 高橋 雄三: "口腔癌に対する抗CD3抗体/IL-2活性化細胞(CD3・LAK)による養子免疫療法" 日本口腔腫瘍学会誌. 4. 112-112 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 森 良之: "口腔癌組織浸潤リンパ球からの抗腫瘍活性の誘導に関する研究" 日本口腔腫瘍学会誌. 4. 209-209 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 湊 秀次: "口腔扁平上皮癌由来樹立細胞株のLAK活性に対する感受性一標的腫瘍細胞上のHLA抗原発現の関連性について" 日本口腔科学会雑誌. 41. 859-860 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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