Induction of cytotoxicity of human tumor-infiltrating lymphocytes against autologous tumor cells and its application for cancer therapy
| Project/Area Number |
63570599
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Okayama University |
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Principal Investigator |
HIZUTA Akio Okayama University Medical School, First Department of Surgery Instructor, 医学部附属病院, 助手 (60199007)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIKAWA Yasuaki Okayama University Medical School, First Department of Surgery Assistant Profess, 医学部附属病院, 講師 (00152851)
ORITA Kunzo Okayama University Medical School, First Department of Surgery Professor, 医学部, 教授 (20033053)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
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| Keywords | Human solid cancer / Tumor-infiltrating lymphocyte / Lymphokine-activated killer (LAK) cell therapy / gammadeltaTCell / Cytotoxicity / linerleukin-2 (IL-2) / Biological response modifier (BRM) / Intratumoral injection / 腫瘍浸潤リンパ球 / ヒト腫瘍 / 養子免疫療法 / 腫瘍細胞障害活性 / γδ型T細胞レセプタ- / ヒト消化器癌 / 細胞表面マーカー / リンホカイン産生能 / 活性化リンパ球移入療法 |
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| Research Abstract |
1) Cancer patients were treated with the adoptive immunotherapy with lymphokine-activated killer (LAK) cells which were induced by culture of autologous peripheral blood lymphocytes (PBL) with interleukin-2(IL-2). Local administration by intraarterial or intracavital infusions of LAK cells produced a superior therapeutic efficacy to systemic administration by intravenous infusions.
2)A half of tumor-infiltrating cells into human solid cancers consisted of T lymphocytes and the proportion of CD8^+T lymphocytes were greater than that of PBL.Tumor-infiltrating lymphocytes (TIL) contained gammadelta T cells and the majority of those cells in colorectal cancers were CD8^+ gammadelta T cells whose lineage was different from that of PBL.Hepatocellular carcinoma contained a greater number of gammadelta TIL than other human solid cancers.
3)Culture of TIL with IL-2 alone was inadequate for their in vitro expansion, and we found that TIL effectively expanded in culture by addition of 20% conditioned medium derived from LAK cell induction.
4)Cytotoxicity against tumor cells was notdetected in freshly isolated TIL.Cytotoxicity of TIL gradually increased in culture, reached its maximum at 2 to 3 weeks, and disappeared at 4 to 7 weeks. Phytohemagglutinin (PHA) was found to be capable of partial restoration of the diminished cytotoxicity of cultured TIL.
5) TIL of advanced gastric cancer were activated in vivo by preoperative intratumoral injection with a biological response modifier, OK-432, and survival of patients after curative sugery was compared with control patients. Although there was no difference in survival of patients with scanty TIL,the activation of TIL improved 3-year survival in patients with TIL of a medium or over degree.
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Report
(3 results)
Research Products
(28 results)
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[Publications] Hizuta, S., Gouchi, A., Okabayashi, Y., Naomoto, Y., Matsuno, T., Kamikawa.Y., and Orita, K.: "Immunotherapy for gastroenterological cancers(in Japanese)" The Japanese Journal of Clinical and Experimental Medicine. 69. 1861-1866 (1992)
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[Publications] Matsumoto, M., Hizuta, A., Miyagi, K., Kawaguchi, H., Kataoka, K., Yamamoto, M., Naomoto, Y., Tanaka, N., and Orita, K.: "Analysis of gammadelta T cells in tumor-infiltrating lymphocytes(in Japanese with English abstract)" Journal of Clinical and Experimental Medicine(IGAKU NO AYUMI). 162. 159-160 (1992)
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[Publications] Hizuta, A., Takahashi, M., Watanabe, N., Iwagaki, H., Tanaka, N., and Orita, K.: "Liver metastasis and local immune responses(in Japanese)" KARKINOS. 6. 307-313 (1993)
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[Publications] Suo, J., Tanaka, N., Hizuta, A., Yunoki, S., and Orita, K.: "Suppression of hepatic natural killer activity by liver metastasis of cancer and restoration of killer activity by oral administration of a Basidomycetes-derived polysaccharide, PSK" Acta Medica Okayama. 48. 237-242 (1994)
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[Publications] Watanabe, N., Hizuta, A., Iwado, H., Gomi, S., Tanaka, N., and Orita, K.: "Flow cytometric analysis of tumor-infiltrating lymphocytes into human colorectal cancer, lymphocytes localized in normal intestine, and peripheral blood lymphocytes (in Japanese)" Digestive organ and Immunology. 30. 195-197 (1995)
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[Publications] Hizuta, A., Yunoki, S., Tatemoto, A., Okamoto, Y., Nagata, Y., Yamamoto, M., Matsumoto, M., Kawaguchi, H., Muro, M., Kataoka, K., Naomoto, Y., Tanaka, N., and Orita, K.: Enhanced therapeutic effect of lymphokine-activated killer (LAK) cells treated with neuraminidase against metastatic liver tumor in mice. In "Frontiers of Mucosal Immunology/Volume 2", eds.M.Tsuchiya, H.Nagura, T., Hibi, and I.Moro. Elservier Science Publishers B.V., Amsterdam, 507-508 (1991)
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[Publications] Hizuta, A., Miyagi, K., Ohno, S., Tanaka, N., and Orita, K.: Immunomodulation by pokeweed mitogen in "Therapeutic Plasmapheresis(XII)", eds.T.Agishi, A.Kawamura, and M.Mineshima. VSP,Utrecht, 651-654 (1993)
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