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Clinical study on immunotherapy with lymphokine-activated killer cells for renal cancer.

Research Project

Project/Area Number 62480339
Research Category

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

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionOsaka University

Principal Investigator

SONODA Takao  Osaka University ・ Professor Faculty of Medicine, 医学部, 教授 (80028290)

Co-Investigator(Kenkyū-buntansha) SUGAO Hideki  Osaka University ・ Assistant Faculty of Medicine, 医学部, 助手 (80154441)
TAKAHARA Shiro  Osaka University ・ Assistant Faculty of Medicine, 医学部, 助手 (70179547)
NAKANO Etsuji  Osaka University ・ Associate Prof. Faculty of Medicine, 医学部, 講師 (90116070)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsRenal cancer / Interleukin 2 / Lymphokine-activated killer cells / adoptive immunotherapy / Interleukin 2 / Lymphokine-activated killer cells / Adoptive immunotherapy / IAK細胞
Research Abstract

In order to examine the utility of interleukin 2 (IL 2) to renal cancer as an immunotherapeutic agent, we used the method of a 4-hour ^<51>chromium-release cytotoxicity assay and showed that peripheral blood lymphocytes (PBLs) stimulated with IL 2 were capable of lysing autologous cultured tumor cells. This finding demonstrated the applicability of adoptive immunotherapy with lymphokine-activated killer (LSK) cells in RCC patients. In the present study, we carried out adoptive immunotherapy with autologous LAK cells in conjunction with systemic administration of IL 2 in patients with advanced RCC. Moreover, in order to investigate the possibility of selection of appropriate candidates for this immunotherapy on the basis of the results of a ^<51>chromium-release cytotoxicity assay employing autologous tumor cells as the target, we looked for a correlation between in vitro autologous tumor cell lysis by LAK cells and the clinical response to the therapy.
Eleven men and 3 women with metast … More atic rcc were entered in this study. They were aged between 37 and 72 years and had undergone nephrectomy for histologically proven RCC. A large number of lymphocytes (PBLs) were separated from lymphocyte-rich fraction obtained from leukaphereses by density centrifugation on ficoll-hypaque. The cells were suspended in 1000 or 2000 ml of RPMI 1640 containing 2 units/ml of IL 3, 50 ug/ml of gentamicin and 5% heat-inactivated human AD serum. After cultivation for 3-4 days, the IL 2-stimulated PBLs (LAK cells) were infused to the patients. In addition, 1000 units of IL 2 were infused once or twice a day. Of 14 patients, a partial response was observed in 3. As toxic symptoms, headache and shaking chills occurred immediately after each infusion of LAK cells. The toxic symptoms of IL 2 probably consisted of fever, edema and eosinophilia. The ^<51>chromum-release cytotoxicity assay employing autologous tumor cells as the target was performed in 6 of the 14 patients. Autologous tumor lysis in the 3 patients showing a partial response was 30.0%, 5.9% and 52.0%. On the other hand, the lung metastases did not respond to the therapy in spite of high autologous tumor cell lysis of more than 90%. Thus, no significant correlation was found between the in vitro assay and the clinical response.
In conclusion, although a complete response could not be obtained, it can be said that this immunotherapy may be effective against RCC, particularly lung metastases, since a partial response was achieved in 3 of 14 patients. However, it should be taken into consideration that this immunotherapeutic approach may risk increasing the frequency of brain metastases. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Nakano,E.;Tada,Y,;Ichikawa,Y.;Fujuoka,H.;Matsuda,M.;Takaha,M.;Sonoda,T.;: Journal of Urology. 137. 641-648 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 中野悦次,松田稔: 泌尿器外科. 1. 195-199 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 中野悦次: 腎と透析.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nakano,E.;Iwasaka,A.;Seguchi,T.;Sugao,H.;Matsuda,M.;Sonoda,T.: Journal of Urology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 中野悦次,多田安温,松田稔,岡田孝人: "泌尿器がん化学療法の進歩と問題点" 蟹書房, 341 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 中野悦次: "腎細胞癌治療の実際" 医薬ジャーナル社, 128 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nakano E.; Taka Y.; Ichikawa Y.; Fujioka H.; Matsuda M.; Takaha M.; Sonoda T.: "Lysis of autologous tumor cells by peripheral blood lymphocytes treated with interleukin 2 in patients with renal cell carcinoma." Jounal of Urology. 137. 641-648 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nakano E.; Iwakaki A.; Seguchi T.; Sugao H.; Matsuda M.; Sonoda T.: "Immunotherapy of metastatic renal cell carcinoma with autologous lymphokine-activated killer cells and interleukin 2." Jounal of Urology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 中野悦次,松田稔: 泌尿器外科. 1. 195-199 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 中野悦次: 腎と透析.

    • Related Report
      1988 Annual Research Report
  • [Publications] Nakano,E.;Iwasaka,A.;Seguchi,T.;Sugao H.;Matsuda,M.;Sonoda,T.: Journal of Urology.

    • Related Report
      1988 Annual Research Report
  • [Publications] 中野悦次: "腎細胞癌治療の実際" 医薬ジャーナル社, 128 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 中野悦次: "がん診療Questions & Answers" 六法出版, (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Nakano E.: Journal of Urology.137. 641-648 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 中野悦次: 泌尿器科外科. 1. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] 中野悦次: "腎癌に対するautologous LAK cellsによるasoptive immuno therapy「泌尿器がん化学療法の進歩と問題点」" 蟹書房, 341 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 中野悦次: "骨細胞癌に対する免疫療法-LAK cellsによるadoptive immuno therapy" 医薬ジャーナル社, 128 (1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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