2002 Fiscal Year Final Research Report Summary
A immunotherapy for primary non small cell lung cancer with Vα24 NKT cells
| Project/Area Number |
11357012
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Thoracic surgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
FUJISAWA Takehiko Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110328)
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| Co-Investigator(Kenkyū-buntansha) |
IIZASA Toshihiko Chiba University, University Hospital, Lecturer, 医学部付属病院, 講師 (10272303)
NAKAYAMA Toshinori Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (50237468)
TANIGUCHI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110310)
MOTOHASHI Shinichirou Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (60345022)
OTSUJI Mizuto Chiba University, University Hospital, Assistant, 医学部付属病院, 助手 (50344982)
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| Project Period (FY) |
1999 – 2002
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| Keywords | Non Small Cell Lung Cancer / Metastasis / Dendritic cell / Immunotherapy / NKT cell |
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| Research Abstract |
Primary lung cancer is hard to cure, even with intensive treatments. Approximately half or more of lung carcinoma patients, even those undergoing complete resection, had clinically undetectable local or distant micrometastases. Since intrapulmonary recurrence is commonly observed during postoperative follow-up of lung cancer, control of intrapulmonary metastases is particularly important for improving prognosis. We reported that α-GalCer-pulsed DCs activated Vαl4 NKT cells and eradicated established metastatic tumor foci in mouse lung metastasis models, and i.v.-injected α-GalCer-pulsed DCs reached to the lung and led to activation of endogenous Vα14 NKT cells. Equivalent amounts of Vα24 NKT cells appeared to exist in the human lung compared to Vα14 NKT cells in the mouse lung, and considerable numbers of Vα24 NKT cells infiltrated in the tumor tissue. This observation also suggests that the reduction of peripheral blood Vα24 NKT cell number is not a significant problem for clinical immunotherapy using α-GalCer-pulsed DCs. Here, we monitored the number of Vα14 NKT cells in the lung of mice receiving α-GalCer-pulsed DCs and found that significantly increased Vα24 NKT cells were sustained . Thus, we may expect similarly potent antitumor effects in humans when α-GalCer-pulsed DCs are administered. Our results suggest that micrometastasis in the lung of patients following radical surgery of cancer can be eradicated when α-GalCer-pulsed DCs are administered. We determined the precise conditions for clinical, application, α-GalCer-pulsed DC therapy might become a new' immunotherapy for lung cancer patients.
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[Publications] Kawano T, Nakayama T, Kamada N, Kaneko Y, Harada M, Ogura N, Akutsu Y, Motohashi S, lizasa T, Endo H, Fujisawa T, Shinkai H, Taniguchl M.: "Anti-tumor cytotoxicity mediated by ligand-activated human Va24 NKT cells"Cancer Res. 59. 5102-5105 (1999)
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