1992 Fiscal Year Final Research Report Summary
Development of Culture system for LAK cells and its application to adoptive immunotheraphy for lung cancer.
| Project/Area Number |
02557049
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KIMURA Genki Kyushu University. Medical Institute of Bioregulation. Professor., 生体防御医学研究所, 教授 (00031964)
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| Co-Investigator(Kenkyū-buntansha) |
NOMOTO Kikuo Kyushu University. Medical Institute of Bioregulation. Professor., 生体防御医学研究所, 教授 (50037355)
SUGIMACHI Keizo Kyushu University. Faculty of Medicine. Professor., 医学部, 教授 (00038762)
TOGAMI Masatoshi Japan Synthetic Robber, Co.LTD.Tsukuba Research Laboratory. Research Associate., 筑波研究所, 主任研究員
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| Project Period (FY) |
1990 – 1992
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| Keywords | LAK cell / LIFROC culture apparatus / Liquid-filled rotatory culture / Lymphokine-activated killer cell / Adopted immunotheraphy / Lymphocyte culture / High-density cell culture / Lung cancer |
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| Research Abstract |
For application with surgical adjuvant therapy of cancer. we have designed a unique regimen of adopuve immunotherapy with lymphokineacuvated killer (LAK) cells and recombinant interleukin-2 (IL-2). The regimen features the prolonged (6 consecutive days) subcutaneous administration of a low-dose IL-2 and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of operations. According to this regimen. 19 patients with pathological stage-1 lung cancer received immunotheraph about 2 weeks after pulmonary lobectomy. Clinical toxicities included fever. fatigue. <5% weight gain. and edema.
All toxicities reversed within 4 days after the complection of therapy. In 13 patients. peripheral blood lymphecytes obtained 24h after therapy exhibited in vitro LAK activity. Thus the regimen is considered to be well-tolerable and immunologically active, in regard to the postoperative state of the patients.
To improve the routine performance of the generation and expansion of LAK cells. we have developed a new culture system (LIFROC Liquid-Filled Rotary Culture : formaly designated JCC device). The LIFROC system is essentially based on dialysis culture. A dialysis membrane divides the culture vessel from the outside circulation of basal medium. The culture vessel is rotated for the proper dispersion of cells and supplied with oxygen through a silicon tube.
With this LIFROC system. the cell density reached a maximum 2.7x10^7 cells/ml with greater than 90% viability and a substantial level of LAK activity. In comparison with a convenstonal batchwise culture system suing tissue culture dishes. the LIFROC system was able to reduce the consumption of basal medium. IL-2. and serum by 20%, 84%, and96%, respectively.
Culture vessel, reservoir, and tools for the recovery of LAK cells from culture medium were devised to be disposable. This culture system is apphed with safe to culture LAK cells for adoptive immunotheraphy.
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Research Products
(34 results)
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[Publications] Murata.M.,Yano,T.,Togami,M.,Yasumoto,K.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "Development of a new culture system for human lymphokine-activated killer cells." J.Immunol.Meth.129(1). 89-95 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yano.T.,Murata.M.,Yoshino,I.,Ishida,T.,Kimura,G.,Sugimachi,K.,and Nomoto,K.: "Effect of an anti-CD3 antibody on the culture of Iymphokine-activated killer cells from human Iymph node Iymphocytes." Cancer J.3(3). 154-158 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yano.T.,Ishida.T.,Yoshino,I.,Murata,M.,Yasumoto,K.,Kimura,G.,Nomoto,K.,and Sugimachi,K.: "A regimen of surgical adjuvant immunotherapy for cancer with interleukin-2 and Iymphokine-activated killer cells." Biotherapy. 3(3). 245-251 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshino,I.,Yano,T.,Yoshikai,Y.,Murata,M.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "Oligoclonal T lymphocytes infiltrating into human lung cancer tissues." Int.J.Cancer. 47(5). 654-658 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshino,I.,Yano,T.,Murata,M.,Ishida,T.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "Cytolytic potential of peripheral blood Iymphocytes following adoptive immunotherapy with Iymphokine-activated killer cells and low-dose interleukin-2" Cancer Res.51(5). 149A-1498 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Togami,M.,Yasumoto,K.,Yano,T.,Ishida,T.,Kimura,G.,Sugimachi,K.,and Nomoto,K.: "Studies of serum-free medium for the generation of Iymphokine-activated killer cells." Cytotechnology. 6(1). 39-47 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yano,T.,Kimura,G.,Hara,N.,Ohta,M.,Sugimachi,K.,and Nomoto,K.: "Cytolytic profiles of interleukin-2 activated Iymphocytes derived from various sites in Iung cancer." Cancer J.4(3). 174-177 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Murata,M.,Yano,T.,Yoshino,l.,Togami,M.,Sogabe,M.,Yasumoto K.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "Development of a new culture system for human Iymphokine-activated killer cells.II.Comparison with a conventional static culture method." Cytotechnology. 7(2). 75-83 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshino,I.,Yano,T.,Murata,M.,Ishida,T.,Sugimachi,K.,Kimura,G.,and Nomoto,K.,: "Tumor-reactive T cells accumulate in lung cancer tissues but fails to respond due to tumor cell-derived factor" Cancer Res.52(3). 775-781 (1992)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshino,I.,Yano,T.,Matsuzaki,G.,Ishida,T.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "T Iymphocytes bearing-type T cell receptor in thymic tumor tissues." J.Nat.Cancer Inst.(submitted).
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshino,I.,Yano,T.,Miyamoto,M.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "Activation and expansion of CD4^+ cells in vitro by a combination of anti-CD3、and anti-CD28 and interleukin-2." Biotherapy. (to be submitted).
Description
「研究成果報告書概要(和文)」より
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[Publications] Yoshino,I.,Yano,T.,Murata,M.,Miyamoto,M.,Ishida,T.,Sugimachi,K.,Kimura,G.,and Nomoto,K.: "Phenotypes of Iymphocytes infiltrating lung cancer tissues and its variation with histological types of cancer." Lung Cancer. (submitted).
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyamoto,M.,Murata,M.,Takenoyama,M.,Yoshino,I.,Togami,M.,Yano,T.,Yasumoto,K.,Sugimachi,K.,Kimura,G.and Nomoto,K: "Development of a new disposable culture system for human Iymphokine-activated killer(LAK)" J.Immunol.Meth.(to be submitted). (1993)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyamoto,M.,Murata,M.,Yoshino,I.,Togami,M.,Yano,T.,Yasumoto,K.,Sugimachi,K.,Kimura,G.and Nomoto,K.: "Development of a new disposable culture system for human lymphokine-activated killer(LAK)cells" Proceedings of the Fifth Annual Meeting of Japanese Association for Animal Cell Technology.H.Murakami,ed.,Kluwer Academic Publishers,Dordrecht,The Netherland.(in press). (1993)
Description
「研究成果報告書概要(和文)」より
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[Publications] Murata, M., Yano, T., Togami, M., Yasumoto, K., Sugimachi, K., Kimura, G., and Nomoto.K.: "Development of a new culture system for human lymphokine-activated killer cells." J.Immunol.Meth.129(1). 89-95 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yano, T., Murata, M., Yoshino, I., Ishida, T., Kimura, G., Sugimachi, K., and Nomoto, K.: "Effect of an anti-CD3 antibody on the culture of lymphokine-activated killer cells from human lymph node lymphocytes." Cancer J.3(3). 154-158 (1990)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yano, T., Ishida, T., Yoshino, L., Murata, M., Yasumoto, K., Kimura, G., Nomoto, K., and Sugimachi, K.: "A regimen of surgical adjuvant immunotherapy for cancer with interleukin-2 and lymphokine-activated killer cells." Biotherapy. 3(3). 245-251 (1991)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yoshino, I., Yano, T., Yoshikai, Y., Murata, M., Sugimachi, K., Kimura, G., and Nomoto, K.: "Oligoclonal T lymphocytes infiltrating into human lung cancer tissues" Int.J.Cancer. 47(5). 654-658 (1991)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yoshino, I., Yano, T., Murata, M., Ishida, T., Sugimachi, K., Kimura, G., and Nomoto, K.: "Cytolytic potential of peripheral blood lymphocytes following adoptive immunotherapy with lymphokine-activated killer cells and low-dose interleukin-2." Cancer REs.51(5). 1494-1498 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Togami, M., Yasumoto, K., Yano, Y., Ishida, T., Kimura, G., Sugimachi, K., and Nomoto, K.: "Studies of serum-free medium for the generation of lymphopkine-activated killer cells." Cytotechnology. 6(1). 39-47 (1991)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yano.T., Kimura, G., Hara, N., Ohta, M., Sugimachi, K., and Nomoto, K.: "Cytolytic profiles of interleukin-2 activated lymphocytes derived from various sites in lung cancer." Cancer J.4(3). 174-177 (1991)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Murata, M., Yano, T., Yoshino, I., Togami, M., Sogabe, M., Yasumoto, K., Sugimachi, K., Kimura, G., and Nomoto, K.: "Development of a new culture system for human lymphokine-activated killer cells. II.Comparison with a conventional static culture method." Cytotechnology. 7(2). 75-83 (1991)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yoshino, I., Yano, Y., Murata, M., Ishida, T., Sugimachi, K., Kimura, G., and Nomoto, K.: "Tumor-reactive T cells accumulate in lung cancer tissues but fails to respond due to tumor cell-derived factor." Cancer Res.52(3). 775-781 (1992)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yoshino, I., Yano, T., Matsuzaki, G., Ishida, T., Sugimachi, K., Kimura, G., and Nomoto, K.: "T lymphocytes bearing-type T cell receptor in thymic tumor tissues." J.Nat.Cancer Inst.(submitted).
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yoshino, I., Yano, T., Miyamoto, M., Sugimachi, K., Kimura, G., and Nomoto, K.: "Activation and expansion of CD4^+ cells in vitro by a combination of anti-cd3, and anti-cd28 and interleukin-2." Biotherapy. (to be submitted).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshino, I., Yano, T., Murata, M., Miyamoto, M., Ishida, T., Sugimachi, K., Kimura, G., and Nomoto, K.: "Phenotypes of lymphocytes infiltrating lung cancer tissues and its variation with histological types of cancer" Lung Cancer. (submitted).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miyamoto, M., Murata, M., Takenoyama, M., Yoshino, I., Togami, M., Yano, T., Yasumoto, K., Sugimachi, K., Kimura, G.and Nomoto, K.: "Development of a new disposable culture system for human lymphokine activated killer (LAK)" J.Immunol.Meth.(to be submitted). (1993)
Description
「研究成果報告書概要(欧文)」より
-
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[Publications] Miyamoto, M., Murata, M., Yoshino, I., Togami, M., Yano, T., Yasumoto, K., Sugimachi, K., Kimura, G.and Nomoto, K.: "Development of a new disposable culture system for human lymphokine-activated killer (LAK) cells" Oroceedings of the Fifth Annual Meeting of Japanese Association for Animal Cell Technology. H.Murakami, ed., Kluwer Academic Publishers, Dordrecht, The Netherland.(in press). (1993)
Description
「研究成果報告書概要(欧文)」より
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