Four cases of oral cancer treated with adoptive immunotherapy (LAK therapy) and radiotherapy
This report describes four cases of oral cancer treated with immunotherapy using lymphokine activated killer (LAK) cells and radiotherapy. In this study, the cytotoxicity and surface phenotype of induced LAK cells were analyzed. Peripheral blood lymphocytes (PBLs) were also analyzed before and after...
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| Published in | Journal of Japanese Society of Oral Oncology Vol. 8; no. 2; pp. 75 - 85 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
Japanese Society of Oral Oncology
1996
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0915-5988 1884-4995 |
| DOI | 10.5843/jsot.8.75 |
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| Abstract | This report describes four cases of oral cancer treated with immunotherapy using lymphokine activated killer (LAK) cells and radiotherapy. In this study, the cytotoxicity and surface phenotype of induced LAK cells were analyzed. Peripheral blood lymphocytes (PBLs) were also analyzed before and after LAK cell infusion into oral cancer patients. Furthermore, the change of the affected part of the tumor using immunohistochemical procedure was observed. PBLs were obtained from oral cancer patients and induced to LAK cells by rIL-2 (Shionogi Pharmaceutical Co, Ltd, 700JRU/ml) and anti-CD3 moAb (25ng/ml) by culturing for 17 to 24 days. Infusions into regional artery of the tumor in patients were 8-fold divided LAK cells obtained by culturing twice, each infusion interval was 2 to 3 days, and 6.2-17×109 LAK cells were infused into each patient. The cytotoxicity was determined in a 4-hour 51Cr release assay and was determined by K-562 cells (E/T=5/1) . Phenotypic characterization was determined by dichromatic flow cytometry using several monoclonal antibodied. The determined cells were LAK cells and PBLs before and after infusion of LAK cells into oral cancer patients. As for results, cytotoxicity of the mean of LAK cells was 74.6%. Cytotoxicity of PBLs between before and after infusion of LAK cells showed the tendency to decrease in in vitro determination. As for phenotypic characterization, CD8+/CD11- cells and CD3+/HLA-DR+ cells were increased with the mean of LAK cells. CD4+ cells were increased, CD8+/CD11-cells, CD3+/HLA-DR+ cells, and CD8+/CD11+ were decreased with the mean of PBLs between before and after infusion of LAK cells. After infusion of LAK cells, infiltration of UCHL-1+ cells and HLA-DR+ cells were increased markedly around the tumor in case 1. |
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| AbstractList | This report describes four cases of oral cancer treated with immunotherapy using lymphokine activated killer (LAK) cells and radiotherapy. In this study, the cytotoxicity and surface phenotype of induced LAK cells were analyzed. Peripheral blood lymphocytes (PBLs) were also analyzed before and after LAK cell infusion into oral cancer patients. Furthermore, the change of the affected part of the tumor using immunohistochemical procedure was observed. PBLs were obtained from oral cancer patients and induced to LAK cells by rIL-2 (Shionogi Pharmaceutical Co, Ltd, 700JRU/ml) and anti-CD3 moAb (25ng/ml) by culturing for 17 to 24 days. Infusions into regional artery of the tumor in patients were 8-fold divided LAK cells obtained by culturing twice, each infusion interval was 2 to 3 days, and 6.2-17×109 LAK cells were infused into each patient. The cytotoxicity was determined in a 4-hour 51Cr release assay and was determined by K-562 cells (E/T=5/1) . Phenotypic characterization was determined by dichromatic flow cytometry using several monoclonal antibodied. The determined cells were LAK cells and PBLs before and after infusion of LAK cells into oral cancer patients. As for results, cytotoxicity of the mean of LAK cells was 74.6%. Cytotoxicity of PBLs between before and after infusion of LAK cells showed the tendency to decrease in in vitro determination. As for phenotypic characterization, CD8+/CD11- cells and CD3+/HLA-DR+ cells were increased with the mean of LAK cells. CD4+ cells were increased, CD8+/CD11-cells, CD3+/HLA-DR+ cells, and CD8+/CD11+ were decreased with the mean of PBLs between before and after infusion of LAK cells. After infusion of LAK cells, infiltration of UCHL-1+ cells and HLA-DR+ cells were increased markedly around the tumor in case 1. |
| Author | Yugawa, Yoshihiro Kose, Akira Shinozuka, Kazuaki Sasakura, Yuuichi Matsumoto, Gouichi Ibuki, Chinatsu Kobori, Minoru Lee, Ushaku Watanabe, Yoshihisa Shindo, Junichi |
| Author_xml | – sequence: 1 fullname: Kobori, Minoru organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Yugawa, Yoshihiro organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Shinozuka, Kazuaki organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Watanabe, Yoshihisa organization: Department of Oral Pathology, Kanagawa Dental College – sequence: 1 fullname: Kose, Akira organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Matsumoto, Gouichi organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Ibuki, Chinatsu organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Lee, Ushaku organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Sasakura, Yuuichi organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College – sequence: 1 fullname: Shindo, Junichi organization: First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College |
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| References | 7) 猪川勉, 江島正郎, 他: 自己あるいは同種癌細胞刺激により誘導された活性化リンパ球の動注法による頭頸部癌養子免疫療法. 癌と化学療法16: 1438-1447, 1989. 25) 小川恭弘: 癌の放射線治療の免疫応答. BIOTHERAPY 4: 1246-1255, 1990. 27) 石原和之, 山崎直也, 他: 皮膚悪性腫瘍に対する養子免疫療法. 第3回JBRM学会公開シンポジウム抄録集28, 1994. 3) 細川真登男, 河田聡: LAK 細胞の腫瘍組織集積性の増強. 細川真登男: 癌の養子免疫療法, オンコロジア社, 東京, 1990, 51-58. 5) Rosenberg, S. A., Lotze, M. T., et al.: A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316: 889-897, 1987 19) Adler, A., Stein, J. A., et al.: Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients. J Biol Resnonse Med. 3: 491-500, 1984. 4) 広戸幾一郎, 竹田千里, 他: 頭頸部がん治療効果判定効果基準 (案) . 日本頭頸部腫瘍学会治療効果判定基準委員会編, 1982, 1-2. 14) 早川直道, 増田毅, 他: 進行性腎癌に対するLAK細胞の動注療法とその効果について. 日本泌尿器科学会雑誌80 (1) : 28-34, 1989. 9) 伊吹千夏: 抗CD3抗体添加rIL-2誘導LAK細胞の抗腫瘍活性に関する研究. 日口外誌39: 1191-1205, 1993. 10) 関根暉彬: 固層化CD3抗体により活性化したT cell (CD3-AT) を用いた養子免疫療法. BIO-THERAPY4: 1606-1613, 1990. 20) 小倉剛: リンフォカインの臨床応用とその問題点. 代謝26: 135-141, 1989. 12) 井廻道夫, 森山貴史, 他: LAK療法. 肝胆膵15: 583-590, 1987. 24) 佐藤雄一: 浸潤リンパ球, 組織球のサブセット同定による肺癌局所の免疫応答の検討. 病理と臨床3: 241-248, 1975. 11) 白岩浩志, 関根暉彬, 他: 固層化CD3抗体およびインターロイキン2によるリンパ球活性化の基礎的検討. BIOTHERAPY4: 427-433, 1990. 6) 高後裕, 坂牧純夫, 他: IL-2-LAK療法の臨床効果の解析. 細川真登男: 癌の養子免疫療法, オンコロジァ社, 東京, 1990, 71-78. 26) 加地亮詞, 岡本正人, 他: 頭頸部癌に対する局所養子免疫療法と放射線治療との併用療法. 日口外誌36: 1720-1729, 1990. 13) 高山孝弘, 峠哲哉, 他: 血漿交換療法併用によるLAK細胞養子免疫療法の臨床効果. BIOTHERA-PY3: 183-187, 1989. 17) 高橋雄三, 森良之, 他: 口腔癌患者に対する養子免疫療法-LAK細胞の腫瘍組織への集積性および体内分布動態の検索- (抄) 日口科誌39: 1270 1990. 18) Komada, M., Sakamoto, Y., et al.: Treatment of malignant ascites with allogeneic and autologous lymphokine-activated killer cells. Gynecol-Oncol 34: 34-37, 1989. 2) 関根暉彬, 垣添忠生, 他: Tumor-infiltranting lymphocytesの培養とadoptive immunotherapyへの応用. 癌と化学療法16: 1469-1473, 1989. 21) 高久史麿: S-6820 (遺伝子組換えヒトインターロイキン2) の臨床第II相試験. BIOTHERAPY3: 796-805, 1989. 28) Osbam, M., Lavin, P, et al.: Effect of autolymphocyte therapy on survial and quality of life in patients with metastatic renal-cell. Lancet 335: 994-998, 1990. 16) 漆崎一郎: 養子免疫療法サイトカインと癌治療. ライフサイエンス, 東京, 1993, 108-139. 23) 石川哮, 猪川勉, 他: 自己あるいは同種癌およびrIL-2刺激誘導キラー細胞の臨床応用. 細川真登男: 癌の養子免疫療法. オンコロジア社, 東京, 1990, 85-90. 15) Lotze, M. T., Line, B. R., et al.: The in vitro distribution of autologous human and murine lymphoid cells grown in T cell grown factor (TCGF) : implications for the adoptive immu-notherapy of tumors. J. Immunol. 125: 1487-1493, 1980. 8) 田中利茂, 木本安彦, 他: LAK細胞増殖および細胞障害活性に対する抗T3 (CD3) モノクローナル抗体OKT-3の影響 (phenotypeからの検討) . BIOTHERAPY 2: 715-720, 1988. 22) 水野和人, 楊河宏章, 他: IL-2/LAK治療に伴うvascular leak syndrome (VLS) の発症機構. 臨床免疫23: 597-601, 1991. 1) Rosenberg, S. A., Lotze, M. T., et al.: Observation on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313: 1485-1492, 1985. |
| References_xml | – reference: 12) 井廻道夫, 森山貴史, 他: LAK療法. 肝胆膵15: 583-590, 1987. – reference: 17) 高橋雄三, 森良之, 他: 口腔癌患者に対する養子免疫療法-LAK細胞の腫瘍組織への集積性および体内分布動態の検索- (抄) 日口科誌39: 1270 1990. – reference: 1) Rosenberg, S. A., Lotze, M. T., et al.: Observation on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313: 1485-1492, 1985. – reference: 7) 猪川勉, 江島正郎, 他: 自己あるいは同種癌細胞刺激により誘導された活性化リンパ球の動注法による頭頸部癌養子免疫療法. 癌と化学療法16: 1438-1447, 1989. – reference: 10) 関根暉彬: 固層化CD3抗体により活性化したT cell (CD3-AT) を用いた養子免疫療法. BIO-THERAPY4: 1606-1613, 1990. – reference: 24) 佐藤雄一: 浸潤リンパ球, 組織球のサブセット同定による肺癌局所の免疫応答の検討. 病理と臨床3: 241-248, 1975. – reference: 23) 石川哮, 猪川勉, 他: 自己あるいは同種癌およびrIL-2刺激誘導キラー細胞の臨床応用. 細川真登男: 癌の養子免疫療法. オンコロジア社, 東京, 1990, 85-90. – reference: 6) 高後裕, 坂牧純夫, 他: IL-2-LAK療法の臨床効果の解析. 細川真登男: 癌の養子免疫療法, オンコロジァ社, 東京, 1990, 71-78. – reference: 19) Adler, A., Stein, J. A., et al.: Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients. J Biol Resnonse Med. 3: 491-500, 1984. – reference: 21) 高久史麿: S-6820 (遺伝子組換えヒトインターロイキン2) の臨床第II相試験. BIOTHERAPY3: 796-805, 1989. – reference: 22) 水野和人, 楊河宏章, 他: IL-2/LAK治療に伴うvascular leak syndrome (VLS) の発症機構. 臨床免疫23: 597-601, 1991. – reference: 14) 早川直道, 増田毅, 他: 進行性腎癌に対するLAK細胞の動注療法とその効果について. 日本泌尿器科学会雑誌80 (1) : 28-34, 1989. – reference: 4) 広戸幾一郎, 竹田千里, 他: 頭頸部がん治療効果判定効果基準 (案) . 日本頭頸部腫瘍学会治療効果判定基準委員会編, 1982, 1-2. – reference: 11) 白岩浩志, 関根暉彬, 他: 固層化CD3抗体およびインターロイキン2によるリンパ球活性化の基礎的検討. BIOTHERAPY4: 427-433, 1990. – reference: 15) Lotze, M. T., Line, B. R., et al.: The in vitro distribution of autologous human and murine lymphoid cells grown in T cell grown factor (TCGF) : implications for the adoptive immu-notherapy of tumors. J. Immunol. 125: 1487-1493, 1980. – reference: 3) 細川真登男, 河田聡: LAK 細胞の腫瘍組織集積性の増強. 細川真登男: 癌の養子免疫療法, オンコロジア社, 東京, 1990, 51-58. – reference: 9) 伊吹千夏: 抗CD3抗体添加rIL-2誘導LAK細胞の抗腫瘍活性に関する研究. 日口外誌39: 1191-1205, 1993. – reference: 2) 関根暉彬, 垣添忠生, 他: Tumor-infiltranting lymphocytesの培養とadoptive immunotherapyへの応用. 癌と化学療法16: 1469-1473, 1989. – reference: 18) Komada, M., Sakamoto, Y., et al.: Treatment of malignant ascites with allogeneic and autologous lymphokine-activated killer cells. Gynecol-Oncol 34: 34-37, 1989. – reference: 8) 田中利茂, 木本安彦, 他: LAK細胞増殖および細胞障害活性に対する抗T3 (CD3) モノクローナル抗体OKT-3の影響 (phenotypeからの検討) . BIOTHERAPY 2: 715-720, 1988. – reference: 5) Rosenberg, S. A., Lotze, M. T., et al.: A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316: 889-897, 1987 – reference: 13) 高山孝弘, 峠哲哉, 他: 血漿交換療法併用によるLAK細胞養子免疫療法の臨床効果. BIOTHERA-PY3: 183-187, 1989. – reference: 27) 石原和之, 山崎直也, 他: 皮膚悪性腫瘍に対する養子免疫療法. 第3回JBRM学会公開シンポジウム抄録集28, 1994. – reference: 16) 漆崎一郎: 養子免疫療法サイトカインと癌治療. ライフサイエンス, 東京, 1993, 108-139. – reference: 26) 加地亮詞, 岡本正人, 他: 頭頸部癌に対する局所養子免疫療法と放射線治療との併用療法. 日口外誌36: 1720-1729, 1990. – reference: 25) 小川恭弘: 癌の放射線治療の免疫応答. BIOTHERAPY 4: 1246-1255, 1990. – reference: 20) 小倉剛: リンフォカインの臨床応用とその問題点. 代謝26: 135-141, 1989. – reference: 28) Osbam, M., Lavin, P, et al.: Effect of autolymphocyte therapy on survial and quality of life in patients with metastatic renal-cell. Lancet 335: 994-998, 1990. |
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| Title | Four cases of oral cancer treated with adoptive immunotherapy (LAK therapy) and radiotherapy |
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