2006 Fiscal Year Final Research Report Summary
Development of new diagnostic and immunotherapeutic methods for patients with cancer
| Project/Area Number |
14104013
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
KAWAKAMI Yutaka Keio University, Department of Medicine, Professor, 医学部, 教授 (50161287)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Tomonobu Keio University, Department of Medicine, Instructor, 医学部, 助手 (20199334)
SAKURAI Toshiharu Keio University, Department of Medicine, Instructor, 医学部, 助手 (20101933)
SUMIMOTO Hidetoshi Keio University, Department of Medicine, Instructor, 医学部, 助手 (00306838)
MATSUZAKI Yuriko Keio University, Department of Medicine, Instructor, 医学部, 助手 (40255435)
KUDO Chie Keio University, Department of Medicine, Instructor, 医学部, 助手 (90424126)
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| Project Period (FY) |
2002 – 2006
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| Keywords | Tumor antigens / Immunotherapy / Colon cancer / Pancreas cancer / DNA chip / Tumor markers / Immune escape / Microsatellite instability |
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| Research Abstract |
We have established basics for development of new diagnostic and therapeutic methods for various cancers of digestive organs. 1) Identification of human tumor antigens and individualized immunotherapy : Various tumor antigens and T cell epitopes were identified by using systematic gene analysis and cDNA cloning using human IgG from immunodeficient mice implanted with human cancer tissues. The analysis of the immune responses revealed importance of individualized immunotherapy. Intratumoral administration of peptide pulsed dendritic cells was developed, and it resulted in induction of strong immune responses and anti-tumor effects through antigen spreading. 2) Immune responses to MSI^+ cancers : The immune response to tumor specific frameshift peptides was found to explain good prognosis of patients with MSI^+ cancers, indicating possible immunotherapy to MSI^+ cancers. The immune response to a cancer-testis antigen CAGE was frequently detected in the patients with MSI^+ cancers, sugges
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ting its use in the immunotherapy. 3) Mechanisms for immune escape of cancer cells : Using newly developed mutation specific viral shRNAs, enhanced MAPK signaling through the BRAF or RAS mutation was found to cause production of multiple immunosuppressive factors, indicating immunotherapy in combination with signal inhibitors. 4) Immunological implications of cancer stem cells and epithelial mescenchymal transition (EMT) : Differential expression of tumor antigens in the established stem like pancreatic cancer SP cells and EMT cells was found. EMT was found to enhance tumor metastasis through immunosuppression. 5) Clinical applications of the identified tumor antigens : IgG Abs for tumor antigens were found to be useful for prognostic diagnosis. Anti-p53 Ab was found to be useful for early diagnosis of colon cancer in the patients with ulcerative colitis. Tumor markers useful for diagnosis of high metastatic ability were identified. The identified tumor antigens and immune-interventions are expected to be evaluated in the future clinical trials. KU-CR4 is a potential target for antibody therapy. Less
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[Journal Article] Development of individualized immunotherapy based on the analysis on anti-tumor immune responses to the human tumor antigens identified using immunological and genetic methods.2007
Author(s)
Kawakami Y, Fujita T, Kudo C, Sakurai T, Udagawa M, Hasegawa G, Ishida A, Kitagawa Y, Tanabe M, Saito M, Izumi Y, Kawamura M, Yaguchi T, Ueda Y, Hayashi E, Wang Q, Tsukamoto N, Matsuzaki Y, Sumimoto H, Takeuchi H, Tanikawa A, H, a M, Amagai M, Kobayashi K, Ikeda Y, Azuma I, Kitajima M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin Cell Wall Skeleton Stimulation.2006
Author(s)
Udagawa M, Kudo-Saito C, Hasegawa G, Yano K, Yamamoto A, Sumimoto H, Yaguchi M, Toda M, Azuma I, Iwai T, Kawakami Y.
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Journal Title
Clin Cancer Res. 12(24)
Pages: 7465-7475
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel cancer testis antigen frequently expressed in pancreatic, lung and endometrial cancers.2006
Author(s)
Okada T, Akada M, Fujita T, Iwata T, Goto Y, Kido K, Okada T, Matsuzaki Y, Kobayashi K, Matsuno S, Sunamura M, Kawakami Y.
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Journal Title
Clin Cancer Res. 12(1)
Pages: 191-197
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A new melanoma antigen FABP7 involved in proliferation and invasion is a potential target for immunotherapy and molecular target therapy.2006
Author(s)
Goto Y, Matsuzaki Y, Kurihara S, Shimizu A, Okada T, Yamamoto K, Murata H, Takata M, Aburatani H, Hoon D, Saida T, Kawakami Y.
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Journal Title
Cancer Res. 66(8)
Pages: 4443-4449
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Frequent immune responses to a cancer/testis antigen, CAGE, in patients with microsatellite instability positive endometrial cancer.2005
Author(s)
Iwata T, Fujita T, Hirao N, Matsuzaki Y, Okada T, Mochimaru H, Susumu N, Matsumoto E, Sugano K, Yamashita N, Nozawa S, Kawakami Y.
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Journal Title
Clinical Cancer Res. 11
Pages: 3949-3957
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polvmvositis.2005
Author(s)
Okada T, Noji S, Goto Y, Iwata T, Fujita T, Okada T, Matsuzaki Y, Kuwana M, Hirakata M, Horii A, Matsushima K, Kawakami Y.
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Journal Title
Int J Cancer 116
Pages: 925-933
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Carbonic anhydrase-II is a tumor vessel endothelium-associated antigen targeted by dendritic cell therapy.2005
Author(s)
Yoshiura K, Nakaoka T, Nishishita T, Sato K, Yamamoto A, Shimada S, Saida T, Kawakami Y, Takahashi T, Fukuda H, Imajoh-Ohmi S, Oyaizu N, Yamashita N.
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Journal Title
Clin Cancer Res. 11(22)
Pages: 8201-8207
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of bladder cancer antigens recoginized by IgG antibodis of a patient with metastatic bladder cancer2004
Author(s)
Ito K, Fujita T, Akada M, Kiniwa Y, Tsukamoto M, Yamamoto A, Matsuzaki Y, Matsushita M, Asano T, Nakamura J, Tachibana M, Hayakawa M, Ikeda H, Murai M, Kawakami Y.
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Journal Title
Int J Cancer. 108
Pages: 712-724
Description
「研究成果報告書概要(欧文)」より
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